Down syndrome (DS) occurs due to triplication of chromosome 21. Individuals with DS face an elevated risk for development of Alzheimer's disease (AD) due to increased amyloid beta (Aβ) resulting from the over‐expression of the amyloid precursor protein found on chromosome 21. Diagnosis of AD among individuals with DS poses particular challenges resulting in an increased focus on alternative diagnostic methods such as blood‐based biomarkers. The aim of this review was to evaluate the current state of the literature of blood‐based biomarkers found in individuals with DS and particularly among those also diagnosed with AD or in prodromal stages (mild cognitive impairment [MCI]). A systematic review was conducted utilizing a comprehensive search strategy. Twenty‐four references were identified, of those, 22 fulfilled inclusion criteria were selected for further analysis with restriction to only plasma‐based biomarkers. Studies found Aβ to be consistently higher among individuals with DS; however, the link between Aβ peptides (Aβ1‐42 and Aβ1‐40) and AD among DS was inconsistent. Inflammatory‐based proteins were more reliably found to be elevated leading to preliminary work focused on an algorithmic approach with predominantly inflammatory‐based proteins to detect AD and MCI as well as predict risk of incidence among DS. Separate work has also shown remarkable diagnostic accuracy with the use of a single protein (NfL) as compared to combined proteomic profiles. This review serves to outline the current state of the literature and highlights the potential plasma‐based biomarkers for use in detecting AD and MCI among this at‐risk population.

中文翻译：

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唐氏综合症和阿尔茨海默病的血液生物标志物：系统评价。

唐氏综合症 (DS) 的发生是由于 21 号染色体的三倍体。患有 DS 的个体面临更高的阿尔茨海默病 (AD) 发展风险，这是由于染色体上发现的淀粉样蛋白前体蛋白的过度表达导致的淀粉样蛋白 (Aβ) 增加21. 诊断 DS 患者的 AD 带来了特殊的挑战，导致人们更加关注替代诊断方法，例如基于血液的生物标志物。本综述的目的是评估在 DS 患者中发现的基于血液的生物标志物的文献现状，特别是那些同时被诊断患有 AD 或处于前驱期（轻度认知障碍 [MCI]）的患者。利用全面的搜索策略进行了系统审查。确定了 24 个参考文献，其中，选择了 22 个满足纳入标准的进一步分析，仅限于基于血浆的生物标志物。研究发现 DS 患者的 Aβ 值始终较高；然而，Aβ 肽（Aβ1-42 和 Aβ1-40）与 DS 之间的 AD 之间的联系并不一致。更可靠地发现基于炎症的蛋白质升高导致初步工作集中在一种算法方法上，该方法主要使用基于炎症的蛋白质来检测 AD 和 MCI 以及预测 DS 的发病风险。与组合蛋白质组学概况相比，单独的工作还表明使用单一蛋白质 (NfL) 具有显着的诊断准确性。这篇综述旨在概述文献的现状，并强调可用于检测该高危人群中 AD 和 MCI 的潜在血浆生物标志物。