Theodorou Aikaterini, Tsantzali Ioanna, Stefanou Maria-Ioanna, Sacco Simona, Katsanos Aristeidis H, Shoamanesh Ashkan, Karapanayiotides Theodoros, Koutroulou Ioanna, Stamati Polyxeni, Werring David J, Cordonnier Charlotte, Palaiodimou Lina, Zompola Christina, Boviatsis Efstathios, Stavrinou Lampis, Frantzeskaki Frantzeska, Steiner Thorsten, Alexandrov Andrei V, Paraskevas Georgios P, Tsivgoulis Georgios
Second Department of Neurology, "Attikon" University Hospital, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, Via Vetoio, Italy.
Eur Stroke J. 2025 Mar;10(1):278-288. doi: 10.1177/23969873241260538. Epub 2024 Jun 13.
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).
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.
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; < 0.0001], Aβ40 levels [RoM: 0.70; 95% CI: 0.63-0.79; < 0.0001] and the ratio Aβ42/Aβ40 [RoM: 0.62; 95% CI: 0.39-0.98; = 0.0438] differentiated CAA from HC. CSF Aβ40 levels [RoM: 0.73; 95% CI: 0.64-0.83; = 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; = 0.0002 and RoM: 1.44; 95% CI: 1.20-1.73; = 0.0014, respectively] and from AD [RoM: 0.65; 95% CI: 0.58-0.72; < 0.0001 and RoM: 0.64; 95% CI: 0.57-0.71; < 0.0001, respectively]. Plasma Aβ42 [RoM: 1.14; 95% CI: 0.89-1.45; = 0.2079] and Aβ40 [RoM: 1.07; 95% CI: 0.91-1.25; = 0.3306] levels were comparable between CAA and HC.
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.
关于脑淀粉样血管病（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（HC）和阿尔茨海默病（AD）患者相比，CAA患者中四种生物标志物[β-淀粉样蛋白（Aβ42和Aβ40）、总tau蛋白（tau）和磷酸化tau蛋白（p-tau）]的水平。
对已发表的研究进行系统综述和荟萃分析，其中还包括一项为期5年的单中心队列研究，该研究提供了有症状散发性CAA与HC和AD患者脑脊液和血浆生物标志物的可用数据。使用基于生物标志物浓度均值比（RoM）的随机效应模型研究生物标志物的比较。RoM < 1和RoM > 1分别表示CAA中生物标志物浓度低于和高于另一人群。
我们确定了9个队列，包括327例CAA患者（平均年龄：71±5岁；女性：45%）、336例HC（平均年龄：65±5岁；女性：45%）和384例AD患者（平均年龄：68±3岁；女性：53%），这些患者有脑脊液生物标志物的可用数据。脑脊液Aβ42水平[RoM：0.47；95%CI：0.36 - 0.62；P < 0.0001]、Aβ40水平[RoM：0.70；95%CI：0.63 - 0.79；P < 0.0001]以及Aβ42/Aβ40比值[RoM：0.62；95%CI：0.39 - 0.98；P = 0.0438]可将CAA与HC区分开来。脑脊液Aβ40水平[RoM：0.73；95%CI：0.64 - 0.83；P = 0.0003]可将CAA与AD区分开来。脑脊液tau和p-tau水平可将CAA与HC区分开来[RoM分别为：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分别为：0.65；95%CI：0.58 - 0.72；P < 0.0001和RoM：0.64；95%CI：0.57 - 0.71；P < 0.0001]。CAA与HC之间血浆Aβ42[RoM：1.14；95%CI：0.89 - 1.45；P = 0.2079]和Aβ40[RoM：1.07；95%CI：0.91 - 1.25；P = 0.3306]水平相当。
与HC和AD相比，CAA具有独特的脑脊液生物标志物模式。与HC和AD相比，CAA中脑脊液Aβ40水平较低，而与HC相比，CAA中tau和p-tau水平较高，但与AD患者相比则较低。
