ArticleNeurology2022
A Pragmatic, Data-Driven Method to Determine Cutoffs for CSF Biomarkers of Alzheimer Disease Based on Validation Against PET Imaging.
Open access · hybridAbstract readValidation Study
In one paragraph
Article in Neurology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
3.6field-weighted citation impact, top 6% 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.
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
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- Brain capillary endothelial-like cells show altered barrier functionality and reduced transport of amyloid β in late-onset Alzheimer disease.Fluids and barriers of the CNS · 2026Article
- Amyloid Probability in Alzheimer Disease From Plasma, Cerebrospinal Fluid, and Amyloid Imaging.Research square · 2026Article
- Hippocampal 1H-MR spectroscopy metabolites are linked to CSF tau pathology in cognitively unimpaired older adults along the Alzheimer's continuum.Neurobiology of aging · 2026Article
- APOE ɛ4 carriership determines a faster plasma p-tau217 progression in Aβ-positive individuals.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Neuropathologic correlates of cognitive impairment in Alzheimer's disease with discordant CSF biomarker profiles: co-pathologies in focus.Acta neuropathologica · 2025Article
- Glia inflammation and cell death pathways drive disease progression in preclinical and early AD.EMBO molecular medicine · 2025Article
- A proteomic signature of vascular dysfunction linked to tauopathy and degeneration in the aging brain.bioRxiv : the preprint server for biology · 2025Article
- Atrophy trajectories in Alzheimer's disease: how sex matters.Alzheimer's research & therapy · 2025Article
- MemScreen: A smartphone application for detection of mild cognitive impairment: A validation study: Smartphone App for MCI Detection.The journal of prevention of Alzheimer's disease · 2025Article
- Acceptable performance of blood biomarker tests of amyloid pathology - recommendations from the Global CEO Initiative on Alzheimer's Disease.Nature reviews. Neurology · 2024Review
- Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals.Alzheimer's research & therapy · 2024Article
- The Alzheimer's Disease Neuroimaging Initiative in the era of Alzheimer's disease treatment: A review of ADNI studies from 2021 to 2022.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- A year in review: brain barriers and brain fluids research in 2022.Fluids and barriers of the CNS · 2023Article
- Association between ATN profiles and mortality in a clinical cohort of patients with cognitive disorders.Alzheimer's research & therapy · 2023Article
- A how-to guide for a precision medicine approach to the diagnosis and treatment of Alzheimer's disease.Frontiers in aging neuroscience · 2023Review
- Time-Dependent Changes in the Biofluid Levels of Neural Injury Markers in Severe Traumatic Brain Injury Patients-Cerebrospinal Fluid and Cerebral Microdialysates: A Longitudinal Prospective Pilot Study.Neurotrauma reports · 2023Article
- Retinal thickness is associated with global cognition and executive function in mild cognitive impairment due to Alzheimer's disease.Journal of Alzheimer's disease reportsArticle
- The Utility of CSF Biomarkers in Diagnosing Alzheimer's Disease: A Thai Cohort Study.Dementia and geriatric cognitive disorders extraArticle
Corrections and comments
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Authors and funding
24 authors at 2 institutions in 4 countries.
Julien DumurgierFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom. julien.dumurgier@inserm.fr.ORCID https://orcid.org/0000-0003-2070-9706
Séverine SabiaFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0003-3109-9720
Henrik ZetterbergFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-4671-6763
Charlotte E TeunissenFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-4061-0837
Bernard HanseeuwFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-3102-6778
Adelina OrellanaFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.
Susanna SchraenFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-7247-4809
Audrey GabelleFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-7648-9194
Mercè BoadaFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0003-2617-3009
Thibaud LebouvierFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-4386-6045
Eline A J WillemseFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.
Emmanuel CognatFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-3521-5832
Agustin RuizFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0003-2633-2495
Claire HourregueFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.
Matthieu LilamandFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-4622-2413
Elodie Bouaziz-AmarFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.
Jean-Louis LaplancheFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.
Sylvain LehmannFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.
Florence PasquierFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0001-9880-9788
Philip ScheltensFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-1046-6408
Kaj BlennowFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-1890-4193
Archana Singh-ManouxFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.ORCID https://orcid.org/0000-0002-1244-5037
Claire PaquetFrom the Université de Paris (J.D., S. Sabia, A.S.-M.), Inserm U1153, Epidemiology of Ageing and Neurodegenerative Diseases; Cognitive Neurology Center (J.D., E.C., C.H., M.L., C.P.), Lariboisiere-Fernand Widal Hospital, AP-HP, Université de Paris, France; Department of Psychiatry and Neurochemistry (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Neurodegenerative Disease (H.Z.), Institute of Neurology, University College London; Dementia Research Institute (H.Z.), London, United Kingdom; Neurochemistry Laboratory (C.E.T., E.A.J.W.), Clinical Chemistry Department, Amsterdam Neuroscience, Amsterdam University Medical Centers, Vrije Universiteit, the Netherlands; Department of Neurology (B.H.), Cliniques Universitaires Saint-Luc, and Institute of Neuroscience (B.H.), Université Catholique de Louvain, Brussels, Belgium; Gordon Center for Medical Imaging (B.H.), Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston; Research Center and Memory Clinic (A.O., M.B., A.R.), Fundació ACE, Institut Català de Neurciències Aplicades, Universitat International de Catalunya, Barcelona; Centro de Investigación biomédica en Red de Enfermedades Neurodegerenativas (CIBERNED) (A.O., A.R.), Madrid, Spain; Univ. Lille (S. Schraen, T.L., F.P.), CHU Lille, Inserm UMR-S 1172, LilNCog (JPARC)-Lille Neurosciences & Cognition, DISTAlz, LiCEND; Department of Neurology (A.G.), Memory Research and Resources Centre, University of Montpellier; Department of Biochemistry and Molecular Biology (E.B.-A., J.-L.L.), Lariboisière Hospital, APHP, Paris; Department of Biochemistry (S.L.), University of Montpellier, France; Alzheimer Center (P.S.), Department of Neurology, VU University Medical Center, Neuroscience Campus Amsterdam, the Netherlands; and Department of Epidemiology and Public Health (A.S.-M.), University College London, United Kingdom.
Alzheimer's Disease Neuroimaging Initiative
Harvard University · USInserm · FR
Funding
Education, socioeconomic status and Aging: transitions from multimorbidity to functional limitations and mortalityR01AG056477 · NIA · UNIVERSITY COLLEGE LONDON · PI KIVIMAKI, MIKA J, SINGH-MANOUX, ARCHANA · 2018 to 2022
$2.8MNIA NIH HHS R01 AG056477
Abstract
BACKGROUND AND
objectivesTo elaborate a new algorithm to establish a standardized method to define cutoffs for CSF biomarkers of Alzheimer disease (AD) by validating the algorithm against CSF classification derived from PET imaging.
methodsLow and high levels of CSF phosphorylated tau were first identified to establish optimal cutoffs for CSF β-amyloid (Aβ) peptide biomarkers. These Aβ cutoffs were then used to determine cutoffs for CSF tau and phosphorylated tau markers. We compared this algorithm to a reference method, based on tau and amyloid PET imaging status (ADNI study), and then applied the algorithm to 10 large clinical cohorts of patients.
resultsA total of 6,922 patients with CSF biomarker data were included (mean [SD] age: 70.6 [8.5] years, 51.0% women). In the ADNI study population (n = 497), the agreement between classification based on our algorithm and the one based on amyloid/tau PET imaging was high, with Cohen's kappa coefficient between 0.87 and 0.99. Applying the algorithm to 10 large cohorts of patients (n = 6,425), the proportion of persons with AD ranged from 25.9% to 43.5%. DISCUSSION: The proposed novel, pragmatic method to determine CSF biomarker cutoffs for AD does not require assessment of other biomarkers or assumptions concerning the clinical diagnosis of patients. Use of this standardized algorithm is likely to reduce heterogeneity in AD classification.
Indexed as
Alzheimer DiseaseBiomarkersAgedAmyloid beta-PeptidesFemaleHumansMalePeptide FragmentsPositron-Emission Tomographytau ProteinsAmyloid beta-PeptidesBiomarkersPeptide Fragmentstau Proteins
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