阿尔茨海默病的表观遗传时钟与纵向血浆生物标志物

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

作者信息

Zhang Bowei, McEvoy Linda K, Nguyen Steve, Espeland Mark A, Rapp Stephen R, Horvath Steve, Lu Ake, LaCroix Andrea Z, Nievergelt Caroline M, Maihofer Adam X, Resnick Susan M, Mielke Michelle M, Beckman Kenneth, Li Danni, Silver Brian, Manson JoAnn E, Ferrucci Luigi, Shadyab Aladdin H

机构信息

Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.

Kaiser Permanente Washington Health Research Institute, Seattle, WA, USA.

出版信息

medRxiv. 2025 Aug 14:2025.08.12.25333453. doi: 10.1101/2025.08.12.25333453.

DOI:10.1101/2025.08.12.25333453

PMID:40832399

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12363716/

Abstract

INTRODUCTION

Chronological 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.

METHODS

In 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.

RESULTS

At 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.

摘要

引言

实足年龄是阿尔茨海默病及相关痴呆症（ADRD）最强的风险因素。然而，相对于实足年龄的加速生物衰老与ADRD病理的关联尚不清楚。

方法

在女性健康倡议记忆研究中，对2366名认知未受损的老年女性队列，我们研究了表观遗传年龄加速（EAA）的五项基线测量指标与血浆ADRD生物标志物15年变化之间的关联。

结果

在基线时，较高的AgeAccelPheno与较低的淀粉样蛋白β42与淀粉样蛋白β40（Aβ42:Aβ40）比值相关，较高的AgeAccelGrim2与神经丝轻链（NfL）升高相关。纵向来看，较高的达尼丁PACE（测量生物衰老速度）与15年内苏氨酸181位点磷酸化tau（p-tau181）、p-tau217、NfL和胶质纤维酸性蛋白（GFAP）的更快增加相关。