CSF and plasma biomarkers in cerebral amyloid angiopathy: A single-center study and a systematic review/meta-analysis.

IF 5.8 3区医学 Q1 CLINICAL NEUROLOGY European Stroke Journal Pub Date : 2024-06-13 DOI:10.1177/23969873241260538

Aikaterini Theodorou, Ioanna Tsantzali, Maria-Ioanna Stefanou, Simona Sacco, Aristeidis H Katsanos, Ashkan Shoamanesh, Theodoros Karapanayiotides, Ioanna Koutroulou, Polyxeni Stamati, David J Werring, Charlotte Cordonnier, Lina Palaiodimou, Christina Zompola, Efstathios Boviatsis, Lampis Stavrinou, Frantzeska Frantzeskaki, Thorsten Steiner, Andrei V Alexandrov, Georgios P Paraskevas, Georgios Tsivgoulis

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引用次数: 0

Abstract

Introduction: There are limited data regarding cerebrospinal fluid (CSF) and plasma biomarkers among patients with Cerebral Amyloid Angiopathy (CAA). We sought to investigate the levels of four biomarkers [β-amyloids (Aβ42 and Aβ40), total tau (tau) and phosphorylated tau (p-tau)] in CAA patients compared to healthy controls (HC) and patients with Alzheimer Disease (AD).

Patients and methods: A systematic review and meta-analysis of published studies, including also a 5 year single-center cohort study, with available data on CSF and plasma biomarkers in symptomatic sporadic CAA versus HC and AD was conducted. Biomarkers' comparisons were investigated using random-effects models based on the ratio of mean (RoM) biomarker concentrations. RoM < 1 and RoM > 1 indicate lower and higher biomarker concentration in CAA compared to another population, respectively.

Results: We identified nine cohorts, comprising 327 CAA patients (mean age: 71 ± 5 years; women: 45%) versus 336 HC (mean age: 65 ± 5 years; women: 45%) and 384 AD patients (mean age: 68 ± 3 years; women: 53%) with available data on CSF biomarkers. CSF Aβ42 levels [RoM: 0.47; 95% CI: 0.36-0.62; p < 0.0001], Aβ40 levels [RoM: 0.70; 95% CI: 0.63-0.79; p < 0.0001] and the ratio Aβ42/Aβ40 [RoM: 0.62; 95% CI: 0.39-0.98; p = 0.0438] differentiated CAA from HC. CSF Aβ40 levels [RoM: 0.73; 95% CI: 0.64-0.83; p = 0.0003] differentiated CAA from AD. CSF tau and p-tau levels differentiated CAA from HC [RoM: 1.71; 95% CI: 1.41-2.09; p = 0.0002 and RoM: 1.44; 95% CI: 1.20-1.73; p = 0.0014, respectively] and from AD [RoM: 0.65; 95% CI: 0.58-0.72; p < 0.0001 and RoM: 0.64; 95% CI: 0.57-0.71; p < 0.0001, respectively]. Plasma Aβ42 [RoM: 1.14; 95% CI: 0.89-1.45; p = 0.2079] and Aβ40 [RoM: 1.07; 95% CI: 0.91-1.25; p = 0.3306] levels were comparable between CAA and HC.

Conclusions: CAA is characterized by a distinct CSF biomarker pattern compared to HC and AD. CSF Aβ40 levels are lower in CAA compared to HC and AD, while tau and p-tau levels are higher in CAA compared to HC, but lower in comparison to AD patients.

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脑淀粉样血管病的脑脊液和血浆生物标志物：一项单中心研究和一项系统综述/元分析。

导言：有关脑淀粉样血管病（CAA）患者脑脊液（CSF）和血浆生物标志物的数据有限。我们试图研究与健康对照组（HC）和阿尔茨海默病（AD）患者相比，CAA 患者脑脊液中四种生物标志物（β-淀粉样蛋白（Aβ42 和 Aβ40）、总 tau（tau）和磷酸化 tau（p-tau））的水平：对已发表的研究（包括一项为期 5 年的单中心队列研究）进行了系统回顾和荟萃分析，这些研究提供了无症状散发性 CAA 与 HC 和 AD 的脑脊液和血浆生物标志物的数据。生物标志物的比较采用基于生物标志物平均浓度比值（RoM）的随机效应模型进行研究。RoM1分别表示与其他人群相比，CAA的生物标志物浓度较低和较高：我们确定了九个队列，包括 327 名 CAA 患者（平均年龄：71 ± 5 岁；女性：45%）与 336 名 HC 患者（平均年龄：65 ± 5 岁；女性：45%）和 384 名 AD 患者（平均年龄：68 ± 3 岁；女性：53%）的 CSF 生物标志物数据。CSF Aβ42 水平[RoM：0.47；95% CI：0.36-0.62；p p = 0.0438]可将 CAA 与 HC 区分开来。CSF Aβ40水平[RoM：0.73；95% CI：0.64-0.83；p = 0.0003]可将CAA与AD区分开来。CSF tau 和 p-tau 水平可将 CAA 与 HC 区分开来 [RoM: 1.71; 95% CI: 1.41-2.09; p = 0.0002 和 RoM: 1.44; 95% CI: 1.20-1.73; p = 0.0014]，也可将 CAA 与 AD 区分开来 [RoM: 0.65；95% CI：0.58-0.72；p p = 0.2079]和 Aβ40 [RoM：1.07；95% CI：0.91-1.25；p = 0.3306]水平在 CAA 和 HC 之间相当.结论：结论：与HC和AD相比，CAA具有独特的CSF生物标志物模式。结论：与HC和AD患者相比，CAA患者的CSF Aβ40水平较低，而与HC患者相比，CAA患者的tau和p-tau水平较高，但与AD患者相比较低。

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来源期刊

European Stroke Journal Multiple-

CiteScore

7.50

自引率

6.60%

发文量

102

期刊介绍： Launched in 2016 the European Stroke Journal (ESJ) is the official journal of the European Stroke Organisation (ESO), a professional non-profit organization with over 1,400 individual members, and affiliations to numerous related national and international societies. ESJ covers clinical stroke research from all fields, including clinical trials, epidemiology, primary and secondary prevention, diagnosis, acute and post-acute management, guidelines, translation of experimental findings into clinical practice, rehabilitation, organisation of stroke care, and societal impact. It is open to authors from all relevant medical and health professions. Article types include review articles, original research, protocols, guidelines, editorials and letters to the Editor. Through ESJ, authors and researchers have gained a new platform for the rapid and professional publication of peer reviewed scientific material of the highest standards; publication in ESJ is highly competitive. The journal and its editorial team has developed excellent cooperation with sister organisations such as the World Stroke Organisation and the International Journal of Stroke, and the American Heart Organization/American Stroke Association and the journal Stroke. ESJ is fully peer-reviewed and is a member of the Committee on Publication Ethics (COPE). Issues are published 4 times a year (March, June, September and December) and articles are published OnlineFirst prior to issue publication.