Evidence map›Paper›PMID 37966285›Full record

Trial reportThe New England journal of medicine2023

Two Phase 3 Trials of Gantenerumab in Early Alzheimer's Disease.

Randall J Bateman, Janice Smith, Michael C Donohue, Paul Delmar, Rachid Abbas, Stephen Salloway, Jakub Wojtowicz, Kaj Blennow, Tobias Bittner, Sandra E Black and 16 more

2 registry-linked trialsOpen access · greenAbstract readRandomized Controlled TrialClinical Trial, Phase III
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 191 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
191citing papers in PubMed, 8 pooled it
43.6field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03443973 phase3terminatednot on this map

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease

TypeinterventionalSponsorHoffmann-La RocheRan2018 to 2022Enrolled975ConditionsAlzheimer DiseaseArmsGantenerumab, Placebo
NCT03444870 phase3terminatednot on this map

A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Efficacy, and Safety Study of Gantenerumab in Patients With Early (Prodromal to Mild) Alzheimer's Disease

TypeinterventionalSponsorHoffmann-La RocheRan2018 to 2023Enrolled1,053ConditionsAlzheimer DiseaseArmsGantenerumab, Placebo
3 · Its place in the literature

Who cites it

191 citing papers in PubMed, 8 syntheses or guidelines pooled it, 249 citations in OpenAlex.

  1. Incidence, severity, and associated risk factors for amyloid-related imaging abnormalities in anti-amyloid monoclonal antibody therapy for early Alzheimer's disease: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
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  9. Longitudinal clinical outcomes after amyloid clearance in aducanumab phase 3 studies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Trial
  10. Volume change with gantenerumab: Impact of amyloid-related imaging abnormalities and amyloid removal.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
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  20. Modified titration of donanemab reduces ARIA risk and maintains amyloid reduction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
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131 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

26 authors at 14 institutions in 9 countries.

Randall J BatemanFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Janice SmithFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Michael C DonohueFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Paul DelmarFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Rachid AbbasFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).ORCID 0000-0002-9737-4548
Stephen SallowayFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Jakub WojtowiczFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Kaj BlennowFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Tobias BittnerFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Sandra E BlackFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Gregory KleinFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Mercè BoadaFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Timo GrimmerFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Akira TamaokaFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Richard J PerryFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
R Scott TurnerFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
David WatsonFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Michael WoodwardFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Angeliki ThanasopoulouFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Christopher LaneFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Monika BaudlerFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Nick C FoxFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Jeffrey L CummingsFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Paulo FontouraFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
Rachelle S DoodyFrom the Department of Neurology, Washington University School of Medicine, St. Louis (R.J.B.); Roche Products, Welwyn Garden City (J.S., C.L.), and the Department of Brain Sciences, Faculty of Medicine, Imperial College London (R.J.P.), and the Dementia Research Centre, Department of Neurodegenerative Disease, and the U.K. Dementia Research Institute, Queen Square Institute of Neurology, University College London (N.C.F.), London - all in the United Kingdom; the Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D.), and Genentech, South San Francisco (T.B., R.S.D.) - both in California; F. Hoffmann-La Roche, Basel, Switzerland (P.D., R.A., J.W., T.B., G.K., A. Thanasopoulou, M. Baudler, P.F., R.S.D.); Butler Hospital and Warren Alpert Medical School, Brown University, Providence, RI (S.S.); the Department of Psychiatry and Neurochemistry, Sahlgrenska Academy, University of Gothenburg, and the Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital - both in Mölndal, Sweden (K.B.); the Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, and the L.C. Campbell Cognitive Neurology Research Unit, Dr. Sandra Black Centre for Brain Resilience and Recovery, Hurvitz Brain Sciences Research Program, Sunnybrook Research Institute, University of Toronto - both in Toronto (S.E.B.); the Ace Alzheimer Center Barcelona, Universitat Internacional de Catalunya, Barcelona, and the Networking Research Center on Neurodegenerative Diseases (CIBERNED), Instituto de Salud Carlos III, Madrid - both in Spain (M. Boada); the Department of Psychiatry and Psychotherapy, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany (T.G.); the Department of Neurology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan (A. Tamaoka); the Department of Neurology, Georgetown University School of Medicine, Washington, DC (R.S.T.); the Alzheimer's Research and Treatment Center, Wellington, FL (D.W.); the Medical and Cognitive Research Unit, Heidelberg Repatriation Hospital, Austin Health, Melbourne, VIC, Australia (M.W.); and the Chambers-Grundy Center for Transformative Neuroscience, Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas, Las Vegas (J.L.C.).
GRADUATE I and II Investigators and the Gantenerumab Study Group
Roche (Switzerland) · CHUK Dementia Research Institute · GBRoche (United Kingdom) · GBAlzheimer’s Disease Neuroimaging Initiative · USBrown University · USGeorgetown University · USInstituto de Salud Carlos III · ESSahlgrenska University Hospital · SESunnybrook Health Science Centre · CATUM Klinikum · DEUniversity of Nevada, Las Vegas · USUniversity of Southern California · USUniversity of Tsukuba · JPWashington University in St. Louis · US

Funding

Trial-Ready Cohort for Preclinical/Prodromal Alzheimer's DiseaseR01AG053798 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI AISEN, PAUL S., CUMMINGS, JEFFREY L. · 2017 to 2022
$39.4M
Renewal of Centers of Biomedical Research Excellence (COBRE) (Phase 2) CNTN - ResubmissionP20GM109025 · NIGMS · CLEVELAND CLINIC FOUNDATION · PI JESSICA KIRKLAND CALDWELL · 2015 to 2026
$22.8M
Alzheimer's Clinical Trial InnOvatioN (ACTION) InitiativeR35AG071476 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI CUMMINGS, JEFFREY L. · 2021 to 2025
$2.9M
Alzheimer's Disease and Related Dementias Innovation Incubator (InnovaTor)R25AG083721 · NIA · UNIVERSITY OF NEVADA LAS VEGAS · PI JEFFREY L. CUMMINGS, Xue K Zhong · 2023 to 2026
$1.0M
NIA NIH HHS R01 AG053798NIA NIH HHS R35 AG071476NIGMS NIH HHS P20 GM109025
6 · The paper itself

Abstract

backgroundMonoclonal antibodies that target amyloid-beta (Aβ) have the potential to slow cognitive and functional decline in persons with early Alzheimer's disease. Gantenerumab is a subcutaneously administered, fully human, anti-Aβ IgG1 monoclonal antibody with highest affinity for aggregated Aβ that has been tested for the treatment of Alzheimer's disease.

methodsWe conducted two phase 3 trials (GRADUATE I and II) involving participants 50 to 90 years of age with mild cognitive impairment or mild dementia due to Alzheimer's disease and evidence of amyloid plaques on positron-emission tomography (PET) or cerebrospinal fluid (CSF) testing. Participants were randomly assigned to receive gantenerumab or placebo every 2 weeks. The primary outcome was the change from baseline in the score on the Clinical Dementia Rating scale-Sum of Boxes (CDR-SB; range, 0 to 18, with higher scores indicating greater cognitive impairment) at week 116.

resultsA total of 985 and 980 participants were enrolled in the GRADUATE I and II trials, respectively. The baseline CDR-SB score was 3.7 in the GRADUATE I trial and 3.6 in the GRADUATE II trial. The change from baseline in the CDR-SB score at week 116 was 3.35 with gantenerumab and 3.65 with placebo in the GRADUATE I trial (difference, -0.31; 95% confidence interval [CI], -0.66 to 0.05; P = 0.10) and was 2.82 with gantenerumab and 3.01 with placebo in the GRADUATE II trial (difference, -0.19; 95% CI, -0.55 to 0.17; P = 0.30). At week 116, the difference in the amyloid level on PET between the gantenerumab group and the placebo group was -66.44 and -56.46 centiloids in the GRADUATE I and II trials, respectively, and amyloid-negative status was attained in 28.0% and 26.8% of the participants receiving gantenerumab in the two trials. Across both trials, participants receiving gantenerumab had lower CSF levels of phosphorylated tau 181 and higher levels of Aβ42 than those receiving placebo; the accumulation of aggregated tau on PET was similar in the two groups. Amyloid-related imaging abnormalities with edema (ARIA-E) occurred in 24.9% of the participants receiving gantenerumab, and symptomatic ARIA-E occurred in 5.0%.

conclusionsAmong persons with early Alzheimer's disease, the use of gantenerumab led to a lower amyloid plaque burden than placebo at 116 weeks but was not associated with slower clinical decline. (Funded by F. Hoffmann-La Roche; GRADUATE I and II ClinicalTrials.gov numbers, NCT03444870 and NCT03443973, respectively.).

Indexed as

Alzheimer DiseaseAntibodies, Monoclonal, HumanizedAgedAged, 80 and overAmyloid beta-PeptidesAntibodies, MonoclonalHumansMiddle AgedPositron-Emission TomographyAmyloid beta-PeptidesAntibodies, MonoclonalAntibodies, Monoclonal, Humanizedgantenerumab

Identifiers

PMID37966285
PMCPMC10794000
OpenAlexW4388688059

What OpenQuestion holds

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.