Zhou Yajing, Sheehan Rory, Guo Lizhi, Strydom Andre
Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK.
Department of Psychology, The Chinese University of Hong Kong, Hong Kong, China.
Alzheimers Dement. 2025 Apr;21(4):e70135. doi: 10.1002/alz.70135.
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.
唐氏综合征（DS）患者患阿尔茨海默病（AD）的风险很高，其AD病理表现与普通人群相似。本研究通过对2017年至2024年10月发表的研究进行系统综述和荟萃分析，在AT(N)框架内评估了DS患者中与AD相关的血液生物标志物。荟萃分析聚焦于血浆淀粉样β蛋白（Aβ）42、Aβ40、总tau蛋白（t-tau）、磷酸化tau蛋白（p-tau）181、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）水平，比较了2109名DS患者和1006名整倍体对照。与整倍体对照相比，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患者中，Aβ42和t-tau水平升高，p-tau181、NfL和GFAP在所有临床亚组中均持续升高。值得注意的是，在临床前AD中，Aβ40和Aβ42/40比值发生显著变化，而在临床AD中t-tau升高。纳入炎症（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DS患者AD的早期检测和监测。要点：我们回顾了58项关于唐氏综合征（DS）血液生物标志物的研究，并对其中18项使用单分子阵列的研究进行了荟萃分析。与对照相比，DS患者的血浆淀粉样β蛋白（Aβ）42、Aβ40、神经丝轻链（NfL）和胶质纤维酸性蛋白（GFAP）水平升高。DS-阿尔茨海默病（AD）患者的Aβ42、总tau蛋白（t-tau）、磷酸化tau蛋白（p-tau）181、NfL和GFAP水平更高。血浆p-tau181、NfL和GFAP在所有临床亚组中均升高。在临床前AD中Aβ40和Aβ42/40比值发生变化；在临床AD中t-tau升高。
