Evidence map›Paper›PMID 40832399›Full record

ArticlemedRxiv : the preprint server for health sciences2025

Epigenetic clocks and longitudinal plasma biomarkers of Alzheimer's disease.

Bowei Zhang, Linda K McEvoy, Steve Nguyen, Mark A Espeland, Stephen R Rapp, Steve Horvath, Ake Lu, Andrea Z LaCroix, Caroline M Nievergelt, Adam X Maihofer and 8 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

18 authors.

Bowei ZhangHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
Linda K McEvoyKaiser Permanente Washington Health Research Institute, Seattle, WA, USA.
Steve NguyenHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
Mark A EspelandDivision of Gerontology and Geriatric Medicine, School of Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Stephen R RappDepartment of Psychiatry and Behavioral Medicine, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Steve HorvathAltos Labs, San Diego, CA, USA.
Ake LuAltos Labs, San Diego, CA, USA.
Andrea Z LaCroixHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
Caroline M NievergeltDepartment of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Adam X MaihoferDepartment of Psychiatry, School of Medicine, University of California San Diego, La Jolla, CA, USA.
Susan M ResnickLaboratory of Behavioral Neuroscience, National Institute on Aging, National Institutes of Health, Baltimore, MD, USA.
Michelle M MielkeDepartment of Epidemiology and Prevention, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Kenneth BeckmanGenomics Center, University of Minnesota, Minneapolis, MN, USA.
Danni LiDepartment of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA.
Brian SilverDepartment of Neurology, UMass Chan Medical School, Worcester, MA, USA.
JoAnn E MansonDivision of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
Luigi FerrucciLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Aladdin H ShadyabHerbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.

Funding

WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0M
Plasma Proteomic Signatures for Alzheimer's Disease and Related DementiasRF1AG079149 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MCEVOY, LINDA KATHLEEN, SHADYAB, ALADDIN · 2022 to 2022
$7.5M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00002 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI WACTAWSKI-WENDE, JEAN · 2021 to 2025
$6.9M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00004 · NHLBI · STANFORD UNIVERSITY · PI STEFANICK, MARCIA · 2021 to 2025
$6.5M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00003 · NHLBI · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA · 2021 to 2025
$5.0M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00005 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI VITOLINS, MARA · 2021 to 2025
$4.2M
The Role of Sex Hormones in Stroke Risk: A Sex-Specific Integrative Omics Analysis in the NHLBI Trans-Omics for Precision Medicine CohortsR01HL164485 · NHLBI · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI Tracy Madsen · 2023 to 2026
$2.5M
Epigenetic Aging Biomarkers of Mild Cognitive Impairment, Alzheimer's Disease and Related Dementias, and Brain AgingR01AG074345 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI SHADYAB, ALADDIN · 2024 to 2025
$1.1M
Plasma proteomic signatures of physical activity and Alzheimer's disease and related dementiasK99AG082863 · NIA · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NGUYEN, STEVE · 2023 to 2024
$206k
NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NHLBI NIH HHS R01 HL164485NIA NIH HHS K99 AG082863NIA NIH HHS R01 AG074345NIA NIH HHS RF1 AG079149WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

introductionChronological age is the strongest risk factor for Alzheimer's disease and related dementias (ADRD). However, the association of accelerated biological aging relative to chronological age with ADRD pathology is unclear.

methodsIn a cohort of 2,366 cognitively unimpaired older women from the Women's Health Initiative Memory Study, we examined associations of five baseline measures of epigenetic age acceleration (EAA) with 15-year changes in plasma ADRD biomarkers.

resultsAt baseline, higher AgeAccelPheno was associated with lower amyloid-β42 to amyloid-β40 (Aβ42:Aβ40) ratio, and higher AgeAccelGrim2 was associated with elevated neurofilament light (NfL). Longitudinally, higher DunedinPACE - which measures the pace of biological aging - was associated with faster increases in phosphorylated tau at threonine 181 (p-tau181), p-tau217, NfL, and glial fibrillary acidic protein (GFAP) over 15 years. DISCUSSION: Accelerated biological aging, particularly as indicated by DunedinPACE, was associated with increasing levels of plasma ADRD biomarkers over time.

Indexed as

Alzheimer’s diseaseamyloid betabiological agingblood biomarkersdementiaepigenetic clocksGFAP, NfLp-tau181p-tau217, plasmawomen’s health

Identifiers

PMID40832399
PMCPMC12363716

What OpenQuestion holds

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Registered trials

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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.