ArticleResearch square2026
Senescence protein signatures predict dementia risk with causal implication for TBCA: a two-cohort study.
Anna Prizment, Saeun Park, Zexi Rao, Shuo Wang, Pamela L Lutsey, Jim Pankow, Shannon M Sullivan, Weihong Tang, Behnam Sabayan, Timothy M Hughes and 9 more
Abstract readPreprint
In one paragraphArticle in Research square, 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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5 · Who and what moneyAuthors and funding
19 authors.
Anna PrizmentUniversity of Minnesota.
Saeun ParkUniversity of Minnesota.
Zexi RaoUniversity of Minnesota.
Shuo WangUniversity of Minnesota.
Pamela L LutseyUniversity of Minnesota.
Jim PankowUniversity of Minnesota.
Shannon M SullivanUniversity of Minnesota.
Weihong TangUniversity of Minnesota.
Behnam SabayanUniversity of Minnesota.
Timothy M HughesWake Forest University School of Medicine.
Keenan A WalkerNational Institute on Aging.
Ruth DubinUniversity of Texas Southwestern Medical Center.
Rajat DeoUniversity of Pennsylvania.
Wendy PostJohns Hopkins University.
Jerome I RotterThe Lundquist Institute for Biomedical Innovation, Harbor-UCLA Medical Center.
Alexis C WoodChildren's Nutrition Research Center at Baylor College of Medicine.
Peter GanzZuckerberg San Francisco General Hospital, University of California.
Weihua GuanUniversity of Minnesota.
Sanaz SedaghatUniversity of Minnesota.
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MARIC Neurocognitive Study (ARIC-NCS) Renewal 2023-2028U01HL096812 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI JOSEF CORESH, THOMAS H MOSLEY · 2010 to 2026
$65.7MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MSubclinical Vascular Contributions to Alzheimer's Disease: The Multi-Ethnic Study of Atherosclerosis (MESA) Multisite Study of AD (Renewal)R01AG058969 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI Timothy M. Hughes, YONGMEI LIU · 2018 to 2026
$33.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MUniversity of Minnesota Clinical and Translational Science Institute (UMN CTSI)UM1TR004405 · NCATS · UNIVERSITY OF MINNESOTA · PI Bruce R Blazar, Damien A Fair · 2023 to 2026
$30.8MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MTHE ATHEROSCLEROSIS RISK IN COMMUNITIES (ARIC) STUDY - COORDINATING CENTER - TASK AREA B.2 AND B.375N92022D00001 · NHLBI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI COUPER, DAVID · 2022 to 2025
$13.7MARIC Neurocognitive Study (ARIC-NCS) Renewal 2 of 5U01HL096917 · NHLBI · UNIVERSITY OF MISSISSIPPI MED CTR · PI MOSLEY, THOMAS H · 2010 to 2018
$11.9MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MNCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCATS NIH HHS UM1 TR004405NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS 75N92022D00001NHLBI NIH HHS 75N92022D00002NHLBI NIH HHS 75N92022D00003NHLBI NIH HHS 75N92022D00004NHLBI NIH HHS 75N92022D00005NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL134320NHLBI NIH HHS R01 HL159081NHLBI NIH HHS U01 HL096812NHLBI NIH HHS U01 HL096814NHLBI NIH HHS U01 HL096899NHLBI NIH HHS U01 HL096902NHLBI NIH HHS U01 HL096917NIA NIH HHS R01 AG058969NIA NIH HHS R21 AG079242NIDDK NIH HHS P30 DK063491NIEHS NIH HHS 75N98025D00022NIEHS NIH HHS 75N98025D00024NIEHS NIH HHS 75N98025D00025NIEHS NIH HHS 75N98025D00026NIEHS NIH HHS 75N98025D00027NIEHS NIH HHS 75N98025D00028
6 · The paper itselfAbstract
Senescence, a key aging mechanism, is linked to disease via the senescence-associated secretory phenotype (SASP), yet its role in dementia remains unclear. We aimed to identify a minimal circulating SASP protein panel to predict incident dementia and identify causally-associated proteins. Among midlife and late-life participants from the Atherosclerosis Risk in Communities (ARIC) study, we developed three weighted SASP protein scores via multivariable Cox proportional hazards or Lasso Cox regression. Cox proportional hazards regression estimated associations between each standardized score (mean = 0; SD = 1) and incident dementia in an independent ARIC sample and validated in the Multi-Ethnic Study of Atherosclerosis (MESA). Mendelian randomization analyses evaluated causal relationships between SASP proteins and dementia risk. Comparable significant associations were observed across scores in ARIC (per 1 SD: HRs: midlife 1.20-1.33; late-life 1.39-1.50) and MESA (midlife: 1.28-1.38; late-life 1.40-1.62), with stronger associations for late-life scores. Tubulin folding cofactor A protein was the only protein causally associated with incident dementia. SASP scores, even with few proteins, are useful dementia biomarkers, and TBCA is a promising therapeutic target.
Indexed as
dementiamendelian randomizationprospective analysisproteomic scoresenescencesenescent-associated secretory phenotype (SASP)
Identifiers
PMID41928789
PMCPMC13042173
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