ArticlemedRxiv : the preprint server for health sciences2026
Orthogonal Contributions of Genetic, Clinical, and Social Determinants of Health Risk Burdens on Alzheimer's Disease Pathophysiology.
Meri Okorie, Xiaqing Jiang, Paulina Tolosa-Tort, Rakshya U Sharma, Alexandra L Clark, Kristine Yaffe, Jennifer S Yokoyama, Shea Andrews
Abstract readPreprint
In one paragraphArticle in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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What it found
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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 registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
8 authors.
Meri OkorieFein Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Xiaqing JiangDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA.
Paulina Tolosa-TortDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA.
Rakshya U SharmaDepartment of Psychiatry and Behavioral Sciences, University of California, San Francisco, San Francisco, CA, USA.
Alexandra L ClarkDepartment of Psychology, University of Texas at Austin, Austin, Texas, USA.
Kristine YaffeFein Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.
Jennifer S YokoyamaDepartment of Neurology and Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0001-7274-2634 Shea AndrewsFein Memory and Aging Center, University of California, San Francisco, San Francisco, CA, USA.ORCID 0000-0002-1921-9470 Funding
The Health & Aging Brain Study - Health Disparities (HABS-HD)U19AG078109 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI Sid E O'Bryant · 2022 to 2026
$181.1MTDP-43 Loss-of-Function: Biology to BiomarkersP01AG019724 · NIA · UNIVERSITY OF PENNSYLVANIA · PI Jennifer Merrilees · 2002 to 2026
$67.2MHealth and Aging Brain among Latino Elders (HABLE-AT(N)) StudyR01AG058533 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI JOHNSON, LEIGH A, O'BRYANT, SID E · 2020 to 2025
$45.4MProject 2: Biomarker Analysis, Non-Genetic Risk Factors, and Their Genetic InteractionsU19AG079774 · NIA · UNIVERSITY OF PENNSYLVANIA · PI HELENA Chang CHUI, Gyungah Jun · 2023 to 2026
$39.4MResearch Education ComponentP30AG062422 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Katherine P Rankin · 2019 to 2026
$36.9MTR&D3: Intrinsic Surface MappingP41EB015922 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI TOGA, ARTHUR W · 2012 to 2022
$14.1MHealth Disparities in Alzheimer's Disease and Mild Cognitive Impairment among Mexican AmericansR01AG054073 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI O'BRYANT, SID E, TOGA, ARTHUR W · 2017 to 2021
$12.6MTau Metabolism in FTD: From Gene Mutations to Molecular Chaperones and Lysosomal ProteasesU54NS123985 · NINDS · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KARCH, CELESTE MARIE · 2021 to 2025
$9.0MUS-South American Initiative for Genetic-Neural-Behavioral Interactions in Human Neurodegenerative ResearchR01AG057234 · NIA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Claudia Duran-Aniotz, Agustin M. Ibanez · 2019 to 2026
$6.1MEpigenetic Risk Factors for AD Age at Onset and Health Disparities: HABLE Epigenetics StudyR01AG070862 · NIA · UNIVERSITY OF NORTH TEXAS HLTH SCI CTR · PI BARBER, ROBERT CLINTON · 2021 to 2025
$3.4MNIA NIH HHS P01 AG019724NIA NIH HHS P30 AG062422NIA NIH HHS R01 AG054073NIA NIH HHS R01 AG057234NIA NIH HHS R01 AG058533NIA NIH HHS R01 AG070862NIA NIH HHS U19 AG078109NIA NIH HHS U19 AG079774NIBIB NIH HHS P41 EB015922NINDS NIH HHS U54 NS123985
6 · The paper itselfAbstract
Importance: Alzheimer's disease (AD) arises from complex interactions among genetic, clinical, and social determinants of health (SDoH) risk factors, yet their independent contributions to underlying AD pathophysiology remain elusive. Objective: To quantify the effects of risk factors across amyloid (Aβ)/tau, neurodegeneration, and cognition. Design: Cross-sectional analysis using structural equation modeling (SEM). Setting: Health and Aging Brain Study-Health Disparities (HABS-HD), a community-based cohort study. Participants: A total of 2,276 participants with demographics, genetic, clinical, and biomarker data from the baseline visit. Exposures: Main Outcomes and Measures: Latent variables representing Aβ/tau pathology (plasma pTau Results: The total analytic sample included 2,276 participants (mean age: 65.3 ± 8.7; non-Hispanic White: 43.0%, non-Hispanic Black: 16.2%, and Latinx/Hispanic adults: 40.8%). Conclusion and Relevance: Genetic risks were primarily associated with Aβ and tau pathology, clinical risks with neurodegeneration, and SDoH risks with cognition, suggesting that risk factors exert differential effects on AD pathophysiology. Future studies investigating additional risk factors and their longitudinal associations with AD pathophysiological changes are warranted.
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PMID42528531
PMCPMC13409223
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