CSF and plasma biomarkers in cerebral amyloid angiopathy: A single-center study and a systematic review/meta-analysis
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 C. Stavrinou, Frantzeska Frantzeskaki, Thorsten Steiner, Andrei V. Alexandrov, Georgios P Paraskevas, Georgios Tsivgoulis
Abstract
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.