Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis

IF 13 1区医学 Q1 CLINICAL NEUROLOGY

Alzheimer's & Dementia Pub Date : 2025-04-12 DOI:10.1002/alz.70135

Yajing Zhou, Rory Sheehan, Lizhi Guo, Andre Strydom

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引用次数: 0

Abstract

Individuals with Down syndrome (DS) are at high risk of Alzheimer's disease (AD), displaying AD pathology similar to the general population. This study evaluated AD-related blood biomarkers in DS within the AT(N) framework through a systematic review and meta-analysis of studies published between 2017 and October 2024. The meta-analysis focused on plasma amyloid beta (Aβ)42, Aβ40, total tau (t-tau), phosphorylated tau (p-tau)181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels, comparing 2109 DS individuals and 1006 euploid controls. Plasma Aβ42, Aβ40, NfL, and GFAP levels were significantly elevated in DS compared to euploid controls, while the Aβ42/40 ratio was reduced. In DS-AD individuals, Aβ42 and t-tau levels were elevated, with p-tau181, NfL, and GFAP consistently high across clinical subgroups. Notably, Aβ40 and the Aβ42/40 ratio changed significantly in preclinical AD, while t-tau increased in clinical AD. Incorporating inflammation (I) markers highlights neuroinflammation's role in DS-AD progression, supporting the blood-based AT(N)I framework for early AD detection and monitoring in DS.

Highlights

We reviewed 58 studies on Down syndrome (DS) blood biomarkers and a meta-analysis of 18 using single molecule array.
Plasma amyloid beta (Aβ)42, Aβ40, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) levels were elevated in DS compared to controls.
DS-Alzheimer's disease (AD) individuals showed higher Aβ42, total tau (t-tau), phosphorylated tau (p-tau)181, NfL, and GFAP levels.
Plasma p-tau181, NfL, and GFAP were elevated across all clinical subgroups.
Aβ40 and Aβ42/40 ratio changed in preclinical AD; t-tau rose in clinical AD.

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唐氏综合征患者阿尔茨海默病的血液生物标志物：系统回顾和荟萃分析

唐氏综合征（DS）患者罹患阿尔茨海默病（AD）的风险很高，其病理表现与普通人群相似。本研究通过对2017年至2024年10月期间发表的研究进行系统回顾和荟萃分析，在AT（N）框架内评估了唐氏综合征患者的AD相关血液生物标志物。荟萃分析主要针对血浆淀粉样β（Aβ）42、Aβ40、总tau（t-tau）、磷酸化tau（p-tau）181、神经丝蛋白轻链（NfL）和胶质纤维酸性蛋白（GFAP）水平，对2109名DS患者和1006名优生对照者进行了比较。与优倍体对照组相比，DS患者的血浆Aβ42、Aβ40、NfL和GFAP水平显著升高，而Aβ42/40比值降低。在DS-AD个体中，Aβ42和t-tau水平升高，而p-tau181、NfL和GFAP水平在各临床亚组中始终较高。值得注意的是，Aβ40和Aβ42/40比值在临床前AD中发生了显著变化，而t-tau在临床AD中有所增加。结合炎症（I）标志物突出了神经炎症在 DS-AD 进展中的作用，支持基于血液的 AT(N)I 框架，用于早期检测和监测 DS 的 AD。研究重点我们回顾了有关唐氏综合征（DS）血液生物标志物的 58 项研究，并使用单分子阵列对 18 项研究进行了荟萃分析。与对照组相比，DS患者血浆淀粉样蛋白β（Aβ）42、Aβ40、神经丝蛋白轻链（NfL）和神经胶质纤维酸性蛋白（GFAP）水平升高。 DS-Alzheimer's 疾病（AD）患者的 Aβ42、总 tau（t-tau）、磷酸化 tau（p-tau）181、NfL 和 GFAP 水平较高。所有临床亚组的血浆 p-tau181、NfL 和 GFAP 均升高。临床前AD患者的Aβ40和Aβ42/40比值发生变化；临床AD患者的t-tau升高。

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来源期刊

Alzheimer's & Dementia 医学-临床神经学

CiteScore

14.50

自引率

5.00%

发文量

299

审稿时长

3 months

期刊介绍： Alzheimer's & Dementia is a peer-reviewed journal that aims to bridge knowledge gaps in dementia research by covering the entire spectrum, from basic science to clinical trials to social and behavioral investigations. It provides a platform for rapid communication of new findings and ideas, optimal translation of research into practical applications, increasing knowledge across diverse disciplines for early detection, diagnosis, and intervention, and identifying promising new research directions. In July 2008, Alzheimer's & Dementia was accepted for indexing by MEDLINE, recognizing its scientific merit and contribution to Alzheimer's research.