Evidence map›Paper›PMID 41388821›Full record

ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025

APOE, ABCA7, and RASGEF1C are associated with earlier onset of amyloid deposition from more than 4000 harmonized positron emission tomography images.

Tonnar Castellano, Ting Chen Wang, Emma Nolan, Yiyang Wu, Mengna Zhang, Michelle Clifton, Vaibhav A Janve, Alaina Durant, Alexis Regelson, Karly Cody and 23 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
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

3 citing papers in PubMed.

  1. Article
  2. Review
  3. Article
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

33 authors.

Tonnar CastellanoVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.ORCID 0009-0008-9480-5497
Ting Chen WangVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Emma NolanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Yiyang WuVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Mengna ZhangVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Michelle CliftonVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Vaibhav A JanveVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Alaina DurantVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Alexis RegelsonVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Karly CodyDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, California, USA.
Theresa HarrisonHelen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California, USA.
Corinne D EngelmanDepartment of Population Health Sciences, University of Wisconsin, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
William JagustHelen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, California, USA.
Marilyn AlbertDepartment of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Sterling JohnsonAlzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Reisa SperlingDepartment of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Murat BilgelLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, Maryland, USA.
Andrew SaykinDepartment of Radiology and Imaging Sciences, Center for Neuroimaging, School of Medicine, Indiana University, Indianapolis, Indiana, USA.
Badri VardarajanDepartment of Neurology, Columbia University Medical Center, New York, New York, USA.
Richard MayeuxDepartment of Neurology, Columbia University Medical Center, New York, New York, USA.
Alzheimer's Disease Neuroimaging Initiative
Tobey BetthauserDepartment of Medicine, University of Wisconsin School of Medicine and Public Health, Health Sciences Learning Center, Madison, Wisconsin, USA.
David A BennettRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Julie SchneiderRush Alzheimer's Disease Center, Rush University Medical Center, Chicago, Illinois, USA.
Phil De JagerTaub Institute for Research on Alzheimer's Disease and The Aging Brain, Columbia University Medical Center, New York, New York, USA.
Vilas MenonTaub Institute for Research on Alzheimer's Disease and The Aging Brain, Columbia University Medical Center, New York, New York, USA.
Duygu TosunDepartment of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, California, USA.
Elizabeth MorminoDepartment of Neurology and Neurological Sciences, Stanford University, Palo Alto, California, USA.
Derek B ArcherVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Logan DumitrescuVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Timothy J HohmanVanderbilt Memory and Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Mary Ellen KoranDepartment of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, Tennessee, USA.ORCID 0000-0002-3322-9114

Funding

Genetic architecture of age of onset of amyloid positivity: Integrating imaging and genetic tools to identify novel drivers of diseaseK76AG088554 · NIA · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Mary Ellen Irene Koran · 2024 to 2026
$729k
Alzheimer's Association AACSF-22-973008Intramural Research Program of the NIA/NIH K76AG088554The Columbia University Alzheimer's Disease Research Center P30AG10161The Columbia University Alzheimer's Disease Research Center P30AG72975The Columbia University Alzheimer's Disease Research Center P50-AG008702.ROS/MAPThe Columbia University Alzheimer's Disease Research Center R01AG15819The Columbia University Alzheimer's Disease Research Center R01AG17917The Columbia University Alzheimer's Disease Research Center U01AG46152The Columbia University Alzheimer's Disease Research Center U01AG61356
6 · The paper itself

Abstract

introductionNew methods estimate amyloid positivity onset age (EAOA) from amyloid positron emission tomography (PET). We explore the genetics of EAOA to identify molecular factors underlying the earliest Alzheimer's disease (AD) changes.

methodsHarmonized amyloid PET data from 4216 participants were used in genome-wide survival, tissue-specific gene expression, and genetic covariance analyses of EAOA.

resultsVariants in apolipoprotein E (APOE), ABCA7, and RASGEF1C associated with earlier EAOA. APOE ε4/ε4 and ε3/ε4 converted 6.3 and 5 years earlier than ε3/ε3, respectively. ε2 was protective against earlier EAOA. rs4147929, an expression quantitative trait locus for ABCA7, associated with a 4 year earlier EAOA. This variant was associated with lower brain expression of ABCA7, which was associated with increased amyloid pathology at autopsy. Multiple immune-related diseases shared genetic covariance with EAOA. DISCUSSION: APOE, ABCA7, and RASGEF1C associated with earlier EAOA, with supporting evidence from tissue-specific expression analyses, offering insights into intervenable targets at early stages of AD. HIGHLIGHTS: Novel methods estimate how long ago a patient converted to amyloid positivity. Estimating this amyloid clock allows us to determine the onset of the earliest Alzheimer's disease changes. We evaluated what genes influence when someone converts to amyloid positivity. Apolipoprotein E (APOE), ABCA7, and RASGEF1C associated with earlier age of amyloid positivity. Genetic results were supported by tissue-specific expression analyses.

Indexed as

Alzheimer DiseaseApolipoproteins EATP-Binding Cassette TransportersBrainras Guanine Nucleotide Exchange FactorsAgedAged, 80 and overAge of OnsetFemaleHumansMalePositron-Emission TomographyABCA7 protein, humanApolipoproteins EATP-Binding Cassette TransportersRASGEF1C protein, humanras Guanine Nucleotide Exchange FactorsABCA7Alzheimer's diseaseamyloidamyloid clearanceapolipoprotein Egeneticsharmonizationpositron emission tomography

Identifiers

PMID41388821
PMCPMC12701365

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.