Trial reportThe New England journal of medicine2023
Trial of Solanezumab in Preclinical Alzheimer's Disease.
Registry-linked trialOpen access · greenAbstract readRandomized Controlled Trial
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 trial NCT02008357 (Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease), which is not on this map. Cited by 272 papers, 6 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
272citing papers in PubMed, 6 pooled it
58.0field-weighted citation impact, top 1% of its field
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.
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.
Anti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4 Study)
Who cites it
272 citing papers in PubMed, 6 syntheses or guidelines pooled it, 331 citations in OpenAlex.
- Association of cognitive impairment and APOE ε4 with Centiloids in Hispanic and non-Hispanic White cohorts.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Pooled it
- Amyloid-beta-targeting monoclonal antibodies for people with mild cognitive impairment or mild dementia due to Alzheimer's disease.The Cochrane database of systematic reviews · 2026Pooled it
- Elevated temporal tau PET predicts faster cognitive decline in women than men: A meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Pooled it
- Updated Appropriate Use Criteria for Amyloid and Tau PET: A Report from the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging Workgroup.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2025Pooled it
- Updated appropriate use criteria for amyloid and tau PET: A report from the Alzheimer's Association and Society for Nuclear Medicine and Molecular Imaging Workgroup.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Critical assessment of anti-amyloid-β monoclonal antibodies effects in Alzheimer's disease: a systematic review and meta-analysis highlighting target engagement and clinical meaningfulness.Scientific reports · 2024Pooled it
- Clinico-biological trajectories stratified by combined tau biomarkers in preclinical Alzheimer's disease.Alzheimer's research & therapy · 2026Trial
- Late-life body mass index and amyloid interaction on cognitive decline in unimpaired older adults.The journal of prevention of Alzheimer's disease · 2026Trial
- Digital memory assessments and plasma pTau217 enable efficient preclinical Alzheimer's trials.The journal of prevention of Alzheimer's disease · 2026Trial
- Safety and efficacy of crenezumab in cognitively unimpaired carriers of the PSEN1The Lancet. Neurology · 2026Trial
- Pulse pressure as a predictor of Alzheimer's disease biomarkers and cognitive decline: The moderating role of APOE ε4.The journal of prevention of Alzheimer's disease · 2025Trial
- Recruitment and retention in a preclinical AD trial: comparisons between academic and non-academic sites.Alzheimer's research & therapy · 2025Trial
- Independent effects of white matter lesion volume and APOE ɛ4 on ARIA-H in A4 Study.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Donanemab in preclinical Alzheimer's disease: Screening and baseline data from TRAILBLAZER-ALZ 3.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Multimodal prognostic modeling of individual cognitive trajectories to enhance trial efficiency in preclinical Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- Changes in Daily Functioning in Association With Tau and Amyloid Among Unimpaired Older Adults With and Without Elevated Amyloid.Neurology · 2025Trial
- Effects of exercise versus usual care on older adults with amnestic mild cognitive impairment: EXERT versus ADNI.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Trial
- INTERCEPT-AD, a phase 1 study of intravenous sabirnetug in participants with mild cognitive impairment or mild dementia due to Alzheimer's disease.The journal of prevention of Alzheimer's disease · 2025Trial
- Atrophy in preclinical Alzheimer's disease maps to a network that predicts longitudinal decline.Molecular psychiatry · 2026Article
- Defining and Measuring Cognitive Decline and Clinical Relevance.Neurology and therapy · 2026Review
212 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
16 authors at 7 institutions in 3 countries.
Reisa A SperlingFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Michael C DonohueFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Rema RamanFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Michael S RafiiFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Keith JohnsonFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Colin L MastersFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Christopher H van DyckFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).ORCID 0000-0003-1779-097X
Takeshi IwatsuboFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Gad A MarshallFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Roy YaariFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Michele ManciniFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Karen C HoldridgeFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Michael CaseFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
John R SimsFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
Paul S AisenFrom the Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Massachusetts General Hospital, Harvard Medical School (R.A.S., G.A.M.), and the Departments of Neurology and Radiology, Massachusetts General Hospital, Harvard Medical School (K.J.) - both in Boston; Alzheimer's Therapeutic Research Institute, Keck School of Medicine, University of Southern California, San Diego (M.C.D., R.R., M.S.R., P.S.A.); the Florey Institute, University of Melbourne, Melbourne, VIC, Australia (C.L.M.); the Departments of Psychiatry, Neurology, and Neuroscience, Yale School of Medicine, New Haven, CT (C.H.D.); the Department of Neuropathology, Graduate School of Medicine, University of Tokyo, Tokyo (T.I.); and Eli Lilly, Indianapolis (R.Y., M.M., K.C.H., M.C., J.R.S.).
A4 Study Team
Eli Lilly (United States) · USUniversity of Southern California · USBrigham and Women's Hospital · USHarvard University · USMassachusetts General Hospital · USThe University of Melbourne · AUYale University · US
Funding
The Alzheimer's Clinical Trial Consortium - Down Syndrome Network (ACTC- DSN)U24AG057437 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Paul S. Aisen, RONALD C PETERSEN · 2018 to 2026
$198.4MTRIAL OF VALPROATE TO ATTENUATE THE PROGRESSION OF ADU01AG010483 · NIA · UNIVERSITY OF ROCHESTER · PI AISEN, PAUL S. · 1991 to 2012
$116.2MYale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9MRECRUITMENT COREU19AG010483 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI FELDMAN, HOWARD · 2013 to 2020
$80.6MUCSD Shiley-Marcos Alzheimer's Disease Research Center P30P30AG062429 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI DOUGLAS R GALASKO · 2019 to 2026
$34.9MResearch Education ComponentP30AG066514 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI NIKOLAOS K ROBAKIS · 2020 to 2026
$31.0MAnti-Amyloid Treatment in Asymptomatic Alzheimer's Disease (A4) Open-Label Extension StudyR01AG063689 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI AISEN, PAUL S., SPERLING, REISA A. · 2019 to 2024
$30.8MYale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2020 to 2026
$30.2MResearch Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Andrew Franklin Teich · 2020 to 2026
$30.1MResearch Education Core FP30AG072977 · NIA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ROBERT J VASSAR · 2021 to 2026
$26.3MUC Davis Alzheimer's Disease Research CenterP30AG072972 · NIA · UNIVERSITY OF CALIFORNIA AT DAVIS · PI LEE-WAY JIN · 2021 to 2026
$25.2MWake Forest University School of Medicine Alzheimer's Disease Research CenterP30AG072947 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI SUZANNE CRAFT · 2021 to 2026
$24.3MNCATS NIH HHS UL1 TR001863NIA NIH HHS K23 AG059888NIA NIH HHS P30 AG062429NIA NIH HHS P30 AG066462NIA NIH HHS P30 AG066508NIA NIH HHS P30 AG066514NIA NIH HHS P30 AG072946NIA NIH HHS P30 AG072947NIA NIH HHS P30 AG072972NIA NIH HHS P30 AG072977NIA NIH HHS R01 AG063689NIA NIH HHS R01AG063689NIA NIH HHS U01 AG010483NIA NIH HHS U19 AG010483NIA NIH HHS U19AG010483NIA NIH HHS U24 AG057437NIA NIH HHS U24AG057437
Abstract
backgroundTrials of monoclonal antibodies that target various forms of amyloid at different stages of Alzheimer's disease have had mixed results.
methodsWe tested solanezumab, which targets monomeric amyloid, in a phase 3 trial involving persons with preclinical Alzheimer's disease. Persons 65 to 85 years of age with a global Clinical Dementia Rating score of 0 (range, 0 to 3, with 0 indicating no cognitive impairment and 3 severe dementia), a score on the Mini-Mental State Examination of 25 or more (range, 0 to 30, with lower scores indicating poorer cognition), and elevated brain amyloid levels on
resultsA total of 1169 persons underwent randomization: 578 were assigned to the solanezumab group and 591 to the placebo group. The mean age of the participants was 72 years, approximately 60% were women, and 75% had a family history of dementia. At 240 weeks, the mean change in PACC score was -1.43 in the solanezumab group and -1.13 in the placebo group (difference, -0.30; 95% confidence interval, -0.82 to 0.22; P = 0.26). Amyloid levels on brain PET increased by a mean of 11.6 centiloids in the solanezumab group and 19.3 centiloids in the placebo group. Amyloid-related imaging abnormalities (ARIA) with edema occurred in less than 1% of the participants in each group. ARIA with microhemorrhage or hemosiderosis occurred in 29.2% of the participants in the solanezumab group and 32.8% of those in the placebo group.
conclusionsSolanezumab, which targets monomeric amyloid in persons with elevated brain amyloid levels, did not slow cognitive decline as compared with placebo over a period of 240 weeks in persons with preclinical Alzheimer's disease. (Funded by the National Institute on Aging and others; A4 ClinicalTrials.gov number, NCT02008357.).
Indexed as
Alzheimer DiseaseAntibodies, Monoclonal, HumanizedAgedAged, 80 and overAmyloid beta-PeptidesBrainFemaleHumansMalePositron-Emission TomographyAmyloid beta-PeptidesAntibodies, Monoclonal, Humanizedsolanezumab
Identifiers
What OpenQuestion holds
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Registered trials
NCT02008357ClinicalTrials.gov
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.