Faculty of Medical Science, Private University in the Principality of Liechtenstein, Triesen, Liechtenstein; Laboratory Dr. Risch, Vaduz, Liechtenstein.
Laboratory Dr. Risch, Vaduz, Liechtenstein; Department of Internal Medicine Spital Grabs, Spitalregion Rheintal Werdenberg Sarganserland, Grabs, Switzerland.
Adv Clin Chem. 2023;116:31-111. doi: 10.1016/bs.acc.2023.05.001. Epub 2023 Jun 9.
There is a need for blood biomarkers to detect individuals at different Alzheimer's disease (AD) stages because obtaining cerebrospinal fluid-based biomarkers is invasive and costly. Plasma phosphorylated tau proteins (p-tau) have shown potential as such biomarkers. This systematic review was conducted according to the PRISMA guidelines and aimed to determine whether quantification of plasma tau phosphorylated at threonine 181 (p-tau181), threonine 217 (p-tau217) and threonine 231 (p-tau231) is informative in the diagnosis of AD. All p-tau isoforms increase as a function of Aβ-accumulation and discriminate healthy individuals from those at preclinical AD stages with high accuracy. P-tau231 increases earliest, followed by p-tau181 and p-tau217. In advanced stages, all p-tau isoforms are associated with the clinical classification of AD and increase with disease severity, with the greatest increase seen for p-tau217. This is also reflected by a better correlation of p-tau217 with Aβ scans, whereas both, p-tau217 and p-tau181 correlated equally with tau scans. However, at the very advanced stages, p-tau181 begins to plateau, which may mirror the trajectory of the Aβ pathology and indicate an association with a more intermediate risk of AD. Across the AD continuum, the incremental increase in all biomarkers is associated with structural changes in widespread brain regions and underlying cognitive decline. Furthermore, all isoforms differentiate AD from non-AD neurodegenerative disorders, making them specific for AD. Incorporating p-tau181, p-tau217 and p-tau231 in clinical use requires further studies to examine ideal cut-points and harmonize assays.
需要血液生物标志物来检测处于不同阿尔茨海默病（AD）阶段的个体，因为获得基于脑脊液的生物标志物具有侵入性且成本高昂。磷酸化tau 蛋白（p-tau）已显示出作为此类生物标志物的潜力。本系统评价是根据 PRISMA 指南进行的，旨在确定定量测定血浆中丝氨酸 181 处磷酸化的 tau（p-tau181）、丝氨酸 217（p-tau217）和丝氨酸 231（p-tau231）是否可用于 AD 的诊断。所有 p-tau 同工型都会随着 Aβ 积累而增加，并以高精度区分健康个体和处于临床前 AD 阶段的个体。p-tau231 最早增加，其次是 p-tau181 和 p-tau217。在晚期，所有 p-tau 同工型均与 AD 的临床分类相关，并随疾病严重程度而增加，p-tau217 的增加最大。这也反映在 p-tau217 与 Aβ 扫描的相关性更好，而 p-tau217 和 p-tau181 与 tau 扫描的相关性相同。然而，在非常晚期，p-tau181 开始趋于平稳，这可能反映了 Aβ 病理的轨迹，并表明与 AD 风险的中间水平相关。在整个 AD 连续体中，所有生物标志物的增量增加与广泛脑区的结构变化和潜在认知能力下降相关。此外，所有同工型均可将 AD 与非 AD 神经退行性疾病区分开来，使其成为 AD 的特异性标志物。在临床应用中纳入 p-tau181、p-tau217 和 p-tau231 需要进一步研究来检查理想的临界点并协调测定。
