Evidence map›Paper›PMID 34002480›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2021

Plasma amyloid β levels are driven by genetic variants near APOE, BACE1, APP, PSEN2: A genome-wide association study in over 12,000 non-demented participants.

Vincent Damotte, Sven J van der Lee, Vincent Chouraki, Benjamin Grenier-Boley, Jeannette Simino, Hieab Adams, Giuseppe Tosto, Charles White, Natalie Terzikhan, Carlos Cruchaga and 30 more

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 2 pooled it
3.2field-weighted citation impact, top 7% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 2 syntheses or guidelines pooled it, 40 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Article
  5. APOE and plasma AD biomarkers: The role of genetic ancestry in Hispanics/Latinos.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  6. Amyloid-beta (1-40) peptide is associated with systemic metabolic health.European journal of clinical investigation · 2026
    Article
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  10. Review
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  15. Review
  16. Artificial intelligence for dementia genetics and omics.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023
    Review
  17. Article
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  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

40 authors at 15 institutions in 5 countries.

Vincent DamotteUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Sven J van der LeeAlzheimer Center Amsterdam, Department of Neurology, Amsterdam Neuroscience, Vrije Universiteit Amsterdam, Amsterdam UMC, Amsterdam, the Netherlands.
Vincent ChourakiUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Benjamin Grenier-BoleyUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Jeannette SiminoGertrude C. Ford MIND Center, Department of Data Science, John D. Bower School of Population Health, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Hieab AdamsDepartments of Epidemiology, Neurology, and Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Giuseppe TostoTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Charles WhiteProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Natalie TerzikhanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Carlos CruchagaDepartment of Psychiatry, Washington University in St. Louis, Saint Louis, Missouri, USA.
Maria J KnolDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Shuo LiDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Susanna SchraenUniversité Lille, CHU-Lille, Inserm, UF de Neurobiologie, CBPG, Lille, France.
Megan L GroveHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Claudia SatizabalDepartment of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Najaf AminDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Claudine BerrINSERM U1061, University of Montpellier, Montpellier, France.
Steven YounkinDepartment of Neuroscience, Mayo Clinic, Jacksonville, Florida, USA.
Alzheimer's Disease Neuroimaging InitiativeUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Rebecca F GottesmanDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Luc BuéeUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Alexa BeiserDepartment of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
David S KnopmanDepartment of Neurology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Andre UitterlindenDepartment of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Charles DeCarliDepartment of Neurology, University of California at Davis, Davis, California, USA.
Jan BresslerHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Anita DeStefanoDepartment of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Jean-François DartiguesBordeaux Population Health Research Center, INSERM, UMR1219, Bordeaux University, Bordeaux, France.
Qiong YangDepartment of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Eric BoerwinkleHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
Christophe TzourioBordeaux Population Health Research Center, INSERM, UMR1219, Bordeaux University, Bordeaux, France.
Myriam FornageHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
M Arfan IkramDepartments of Epidemiology, Neurology, and Radiology and Nuclear Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.
Philippe AmouyelUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Phil de JagerProgram in Translational NeuroPsychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Christiane ReitzTaub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University, New York, New York, USA.
Thomas H MosleyDepartment of Medicine, Gertrude C. Ford MIND Center, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Jean-Charles LambertUniv. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, Lille, France.
Sudha SeshadriDepartment of Neurology, Boston University School of Medicine, Boston, Massachusetts, USA.
Cornelia M van DuijnDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Boston University · USErasmus MC · NLInserm · FRBroad Institute · USInstitut Pasteur de Lille · FRJohns Hopkins University · USUniversity of Mississippi Medical Center · USBrigham and Women's Hospital · USColumbia University · USGhent University Hospital · BEJacksonville College · USMayo Clinic · USThe University of Texas Health Science Center at Houston · USUniversity of California, Davis · USWashington University in St. Louis · US

Funding

Alzheimer's Disease Neuroimaging Initiative - SupplementU01AG024904 · NIA · NORTHERN CALIFORNIA INSTITUTE RES &EDUC · PI WEINER, MICHAEL W · 2004 to 2015
$121.0M
Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
THE FRAMINGHAM HEART STUDYN01HC25195 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI RAMACHANDRAN, VASAN S · 2007 to 2014
$83.8M
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7M
Research Education CoreP30AG066462 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Miguel Arce · 2020 to 2026
$30.1M
PRECURSORS OF STROKE INCIDENCE AND PROGNOSISR01NS017950 · NINDS · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Hugo Javier Aparicio, Jose Rafael Romero · 1985 to 2026
$22.9M
VASCULAR FACTORS AND MILD COGNITIVE IMPAIRMENT AND ALZHEIMER'S DISEASEP01AG007232 · NIA · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI SCHUPF, NICOLE · 1989 to 2008
$21.7M
Genome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2M
EPIDEMIOLOGY OF DEMENTIA IN THE FRAMINGHAM STUDYR01AG008122 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI AU, RHODA, SESHADRI, SUDHA · 1989 to 2015
$14.4M
Temporal Trends, Novel Imaging and Molecular Characterization of Preclinical and Clinical Alzheimer's Disease in the Framingham CohortsR01AG054076 · NIA · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI DECARLI, CHARLES, SESHADRI, SUDHA · 2016 to 2020
$12.3M
ARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5U01HL096917 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI MOSLEY, THOMAS H · 2010 to 2018
$11.9M
CIHRNCATS NIH HHS UL1 TR001873NCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHLBI NIH HHS HHSN268201100005CNHLBI NIH HHS HHSN268201100005GNHLBI NIH HHS HHSN268201100005INHLBI NIH HHS HHSN268201100006CNHLBI NIH HHS HHSN268201100007CNHLBI NIH HHS HHSN268201100007INHLBI NIH HHS HHSN268201100008CNHLBI NIH HHS HHSN268201100008INHLBI NIH HHS HHSN268201100009CNHLBI NIH HHS HHSN268201100009INHLBI NIH HHS HHSN268201100010CNHLBI NIH HHS HHSN268201100011CNHLBI NIH HHS HHSN268201100011INHLBI NIH HHS HHSN268201100012CNHLBI NIH HHS HHSN268201500001CNHLBI NIH HHS HHSN268201500001INHLBI NIH HHS N01HC25195NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL070825NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL105756NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NIA NIH HHS K24 AG045334NIA NIH HHS K99 AG042483NIA NIH HHS P01 AG007232NIA NIH HHS P30 AG066462NIA NIH HHS R00 AG042483NIA NIH HHS R01 AG008122NIA NIH HHS R01 AG033040NIA NIH HHS R01 AG033193NIA NIH HHS R01 AG034189NIA NIH HHS R01 AG037212NIA NIH HHS R01 AG049607NIA NIH HHS R01 AG054076NIA NIH HHS R56 AG034189NIA NIH HHS RF1 AG054023NIA NIH HHS U01 AG024904NIA NIH HHS U01 AG049505NINDS NIH HHS R01 NS017950NINDS NIH HHS R01 NS087541
6 · The paper itself

Abstract

introductionThere is increasing interest in plasma amyloid beta (Aβ) as an endophenotype of Alzheimer's disease (AD). Identifying the genetic determinants of plasma Aβ levels may elucidate important biological processes that determine plasma Aβ measures.

methodsWe included 12,369 non-demented participants from eight population-based studies. Imputed genetic data and measured plasma Aβ1-40, Aβ1-42 levels and Aβ1-42/Aβ1-40 ratio were used to perform genome-wide association studies, and gene-based and pathway analyses. Significant variants and genes were followed up for their association with brain positron emission tomography Aβ deposition and AD risk.

resultsSingle-variant analysis identified associations with apolipoprotein E (APOE) for Aβ1-42 and Aβ1-42/Aβ1-40 ratio, and BACE1 for Aβ1-40. Gene-based analysis of Aβ1-40 additionally identified associations for APP, PSEN2, CCK, and ZNF397. There was suggestive evidence for interaction between a BACE1 variant and APOE ε4 on brain Aβ deposition. DISCUSSION: Identification of variants near/in known major Aβ-processing genes strengthens the relevance of plasma-Aβ levels as an endophenotype of AD.

Indexed as

AmyloidGenome-Wide Association StudyHealthy VolunteersAlzheimer DiseaseAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesApolipoproteins EAspartic Acid EndopeptidasesBrainHumansPositron-Emission TomographyPresenilin-2AmyloidAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesApoE protein, humanApolipoproteins EAspartic Acid EndopeptidasesBACE1 protein, humanPresenilin-2PSEN2 protein, humanAlzheimer's diseaseAPOEAPPBACE1endophenotypegenetic epidemiologygenome-wide association studyplasma amyloid beta levelsplasma biomarkerspreclinical biomarkersPSEN2

Identifiers

PMID34002480
PMCPMC8597077
OpenAlexW3161336068

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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.