脑淀粉样血管病的核心脑脊液生物标志物谱：一项荟萃分析。

Core cerebrospinal fluid biomarker profile in cerebral amyloid angiopathy: A meta-analysis.

机构信息

From the Stroke Research Center (A.C., S.M.G., A.V.), Massachusetts General Hospital, Harvard Medical School, Boston; Department of Medicine (J.O.F.) and Interdepartmental Division of Critical Care (J.O.F.), University of Toronto; and Critical Care and Medicine Departments and Li Ka Shing Knowledge Institute (J.O.F.), St. Michael's Hospital, Toronto, Canada.

出版信息

Neurology. 2018 Feb 27;90(9):e754-e762. doi: 10.1212/WNL.0000000000005030. Epub 2018 Jan 31.

DOI:10.1212/WNL.0000000000005030

PMID:29386280

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5837868/

Abstract

OBJECTIVE

To perform a meta-analysis of 4 core CSF biomarkers (β-amyloid [Aβ]42, Aβ40, total tau [t-tau], and phosphorylated tau [p-tau]) to assess which of these are most altered in sporadic cerebral amyloid angiopathy (CAA).

METHODS

We systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting amyloid precursor protein metabolism (Aβ42, Aβ40), neurodegeneration (t-tau), and tangle pathology (p-tau) in symptomatic sporadic CAA cohorts vs controls and patients with Alzheimer disease (AD). Biomarker performance was assessed in random-effects meta-analysis based on ratio of mean (RoM) biomarker concentrations: (1) in patients with CAA vs healthy controls and (2) in patients with CAA vs patients with AD. RoM >1 indicates higher biomarker concentration in patients with CAA vs comparison population and RoM <1 indicates higher concentration in comparison groups.

RESULTS

Three studies met inclusion criteria. These comprised 5 CAA patient cohorts (n = 59 patients) vs healthy controls (n = 94 cases) and AD cohorts (n = 158). Three core biomarkers differentiated CAA from controls: CSF Aβ42 (RoM 0.49, 95% confidence interval [CI] 0.38-0.64, < 0.003), Aβ40 (RoM 0.70, 95% CI 0.63-0.78, < 0.0001), and t-tau (RoM 1.54, 95% CI 1.15-2.07, = 0.004); p-tau was marginal (RoM 1.24, 95% CI 0.99-1.54, = 0.062). Differentiation between CAA and AD was strong for CSF Aβ40 (RoM 0.76, 95% CI 0.69-0.83, < 0.0001), but not Aβ42 (RoM 1.00; 95% CI 0.81-1.23, = 0.970). For t-tau and p-tau, average CSF ratios in patients with CAA vs patients with AD were 0.63 (95% CI 0.54-0.74, < 0.0001) and 0.60 (95% CI 0.50-0.71, < 0.0001), respectively.

CONCLUSION

Specific CSF patterns of Aβ42, Aβ40, t-tau, and p-tau might serve as molecular biomarkers of CAA, but analyses in larger CAA cohorts are needed.

摘要

目的

通过对 4 种核心 CSF 生物标志物（β-淀粉样蛋白 [Aβ]42、Aβ40、总 tau [t-tau]和磷酸化 tau [p-tau]）进行荟萃分析，评估这些标志物在散发性脑淀粉样血管病（CAA）中改变最明显的是哪一种。

方法

我们系统地在 PubMed 上搜索了报告反映淀粉样前体蛋白代谢（Aβ42、Aβ40）、神经退行性变（t-tau）和缠结病理（p-tau）的 CSF 生物标志物数据的合格研究，这些数据来自有症状的散发性 CAA 队列与对照组和阿尔茨海默病（AD）患者。基于平均比值（RoM）生物标志物浓度对生物标志物的性能进行随机效应荟萃分析：（1）在 CAA 患者与健康对照组之间；（2）在 CAA 患者与 AD 患者之间。RoM >1 表示 CAA 患者与比较人群相比，生物标志物浓度更高，RoM <1 表示比较组中生物标志物浓度更高。

结果

有 3 项研究符合纳入标准。这些研究包括 5 个 CAA 患者队列（n = 59 例患者）与健康对照组（n = 94 例）和 AD 队列（n = 158 例）。3 种核心生物标志物可区分 CAA 与对照组：CSF Aβ42（RoM 0.49，95%置信区间 [CI] 0.38-0.64，<0.003）、Aβ40（RoM 0.70，95% CI 0.63-0.78，<0.0001）和 t-tau（RoM 1.54，95% CI 1.15-2.07，= 0.004）；p-tau 为边缘（RoM 1.24，95% CI 0.99-1.54，= 0.062）。CSF Aβ40 对 CAA 与 AD 的区分能力较强（RoM 0.76，95% CI 0.69-0.83，<0.0001），但 Aβ42 则不然（RoM 1.00；95% CI 0.81-1.23，= 0.970）。对于 t-tau 和 p-tau，CAA 患者与 AD 患者的平均 CSF 比值分别为 0.63（95% CI 0.54-0.74，<0.0001）和 0.60（95% CI 0.50-0.71，<0.0001）。