美国中西部阿米什人群中的阿尔茨海默病血浆生物标志物

Alzheimer Disease Plasma Biomarkers in the Mid-Western Amish.

作者信息

Wang Ping, Song Yeunjoo E, Lynn Audrey, Miskimen Kristy, Gulyayev Alex, Prough Michael B, Dorfsman Daniel A, Laux Renee A, Fuzzell Sarada L, Hochstetler Sherri D, Zaman Andrew F, Adams Larry D, Caywood Laura J, Clouse Jason E, Herington Sharlene D, Whitehead Patrice, Liu Yining, Moore Noel, Ogrocki Paula, Lerner Alan J, Griswold Anthony J, Vance Jeffery M, Cuccaro Michael L, Scott William K, Pericak-Vance Margaret A, Haines Jonathan L

出版信息

medRxiv. 2025 Jan 3:2024.12.23.24319579. doi: 10.1101/2024.12.23.24319579.

DOI:10.1101/2024.12.23.24319579

PMID:39802805

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11722471/

Abstract

INTRODUCTION

Alzheimer disease (AD) plasma biomarkers are noninvasive measures of the key amyloid beta (Aβ) and tau pathologies. Validation and generalization studies are needed to fully understand their potential for AD prediction and diagnosis in the elderly population.

METHODS

In 1,067 Amish individuals aged ≥ 65, we measured plasma Aβ and tau to assess their relationships with AD-related outcomes.

RESULTS

Among Amish individuals with AD, plasma p-tau181 was significantly higher ( = 0.04), and plasma Aβ42/p-tau181 ratio was significantly lower ( = 0.01) than cognitively normal individuals. The association of AD with elevated p-tau181 was driven by APOE ε4 carriers (OR = 6.02, < 0.001). Cluster analysis identified two subgroups defined by differing Aβ and tau levels, with the high-risk cluster having more APOE ε4 carriers ( < 0.001).

DISCUSSION

Plasma biomarkers, particularly p-tau181, Aβ42/Aβ40, and Aβ42/p- tau181 ratio, are promising surrogate biomarkers for AD-related pathology and clinical outcomes in the Amish.

摘要

引言

阿尔茨海默病（AD）血浆生物标志物是关键淀粉样蛋白β（Aβ）和tau病理的非侵入性测量指标。需要进行验证和推广研究，以充分了解它们在老年人群中预测和诊断AD的潜力。

方法

在1067名年龄≥65岁的阿米什人中，我们测量了血浆Aβ和tau，以评估它们与AD相关结局的关系。

结果

在患有AD的阿米什人中，血浆磷酸化tau181（p-tau181）显著更高（P = 0.04），血浆Aβ42/p-tau181比值显著更低（P = 0.01），与认知正常个体相比。AD与p-tau181升高的关联由APOE ε4携带者驱动（比值比 = 6.02，P < 0.001）。聚类分析确定了由不同Aβ和tau水平定义的两个亚组，高风险亚组有更多的APOE ε4携带者（P < 0.001）。