基于血液的 tau 生物标志物在轻度认知障碍和阿尔茨海默病中的应用：系统评价和荟萃分析。

Utility of Blood-Based Tau Biomarkers for Mild Cognitive Impairment and Alzheimer's Disease: Systematic Review and Meta-Analysis.

机构信息

Institute of Medical Sciences, University of Aberdeen, Aberdeen AB25 2ZD, UK.

Scottish Biologics Facility, University of Aberdeen, Aberdeen AB25 2ZP, UK.

出版信息

Cells. 2023 Apr 18;12(8):1184. doi: 10.3390/cells12081184.

OBJECTIVES

With the development of new technologies capable of detecting low concentrations of Alzheimer's disease (AD) relevant biomarkers, the idea of a blood-based diagnosis of AD is nearing reality. This study aims to consider the evidence of total and phosphorylated tau as blood-based biomarkers for mild cognitive impairment (MCI) and AD when compared to healthy controls.

METHODS

Studies published between 1 January 2012 and 1 May 2021 (Embase and MEDLINE databases) measuring plasma/serum levels of tau in AD, MCI, and control cohorts were screened for eligibility, including quality and bias assessment via a modified QUADAS. The meta-analyses comprised 48 studies assessing total tau (t-tau), tau phosphorylated at threonine 181 (p-tau181), and tau phosphorylated at threonine 217 (p-tau217), comparing the ratio of biomarker concentrations in MCI, AD, and cognitively unimpaired (CU) controls.

RESULTS

Plasma/serum p-tau181 (mean effect size, 95% CI, 2.02 (1.76-2.27)) and t-tau (mean effect size, 95% CI, 1.77 (1.49-2.04)) were elevated in AD study participants compared to controls. Plasma/serum p-tau181 (mean effect size, 95% CI, 1.34 (1.20-1.49)) and t-tau (mean effect size, 95% CI, 1.47 (1.26-1.67)) were also elevated with moderate effect size in MCI study participants compared to controls. p-tau217 was also assessed, albeit in a small number of eligible studies, for AD vs. CU (mean effect size, 95% CI, 1.89 (1.86-1.92)) and for MCI vs. CU groups (mean effect size, 95% CI, 4.16 (3.61-4.71)).

CONCLUSIONS

This paper highlights the growing evidence that blood-based tau biomarkers have early diagnostic utility for Alzheimer's disease.

REGISTRATION

PROSPERO No. CRD42020209482.

目的

随着能够检测阿尔茨海默病（AD）相关生物标志物低浓度的新技术的发展，基于血液的 AD 诊断的想法已接近现实。本研究旨在考虑总tau 和磷酸化 tau 作为血液生物标志物，用于轻度认知障碍（MCI）和 AD 与健康对照组的比较。

方法

筛选了 2012 年 1 月 1 日至 2021 年 5 月 1 日（Embase 和 MEDLINE 数据库）发表的研究，以评估 AD、MCI 和对照组队列中 tau 的血浆/血清水平，包括通过改良 QUADAS 进行质量和偏倚评估。meta 分析包括 48 项研究，评估了总 tau（t-tau）、磷酸化 tau 181 位苏氨酸（p-tau181）和磷酸化 tau 217 位苏氨酸（p-tau217），比较了 MCI、AD 和认知正常（CU）对照组中生物标志物浓度的比值。

结果

与对照组相比，AD 研究参与者的血浆/血清 p-tau181（平均效应大小，95%CI，2.02（1.76-2.27））和 t-tau（平均效应大小，95%CI，1.77（1.49-2.04））升高。与对照组相比，MCI 研究参与者的血浆/血清 p-tau181（平均效应大小，95%CI，1.34（1.20-1.49））和 t-tau（平均效应大小，95%CI，1.47（1.26-1.67））也升高，且具有中等效应大小。p-tau217 也进行了评估，尽管在合格研究中数量较少，用于 AD 与 CU（平均效应大小，95%CI，1.89（1.86-1.92））和 MCI 与 CU 组（平均效应大小，95%CI，4.16（3.61-4.71））。