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Meta-Analysis
. 2025 Mar;10(1):278-288.
doi: 10.1177/23969873241260538. Epub 2024 Jun 13.

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

Aikaterini Theodorou  1 , Ioanna Tsantzali  1 , Maria-Ioanna Stefanou  1 , Simona Sacco  2 , Aristeidis H Katsanos  3 , Ashkan Shoamanesh  3 , Theodoros Karapanayiotides  4 , Ioanna Koutroulou  4 , Polyxeni Stamati  5 , David J Werring  6 , Charlotte Cordonnier  7 , Lina Palaiodimou  1 , Christina Zompola  1 , Efstathios Boviatsis  8 , Lampis Stavrinou  8 , Frantzeska Frantzeskaki  9 , Thorsten Steiner  10 , Andrei V Alexandrov  11 , Georgios P Paraskevas  1 , Georgios Tsivgoulis  1   12
Affiliations
Meta-Analysis

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

Aikaterini Theodorou et al. Eur Stroke J. 2025 Mar.

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.

Keywords: Cerebral amyloid angiopathy; amyloid-β; biomarkers; cerebrospinal fluid; plasma; tau-protein.

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Conflict of interest statement

Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Graphical abstract
Graphical abstract
Figure 1.
Figure 1.
Mean levels of Aβ42, Aβ40, tau, and p-tau among patients with CAA, HC, and patients with AD in the overall meta-analysis.
Figure 2.
Figure 2.
(a) Ratios for CSF Aβ42, (b) Aβ40, (c) Aβ42/Aβ40, (d) total tau (t-tau), and (e) phosphorylated tau (p-tau) levels, of CAA patients to HC.
Figure 3.
Figure 3.
(a) Ratios for CSF Aβ42, (b) Aβ40, (c) Aβ42/Aβ40, (d) total tau (t-tau), and (e) phosphorylated tau (p-tau) levels, of CAA patients to AD patients.
Figure 4.
Figure 4.
(a) Ratios for plasma Aβ42, and (b) and Aβ40 levels, of CAA patients to HC.
See this image and copyright information in PMC

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References

    1. Charidimou A, Boulouis G, Gurol ME, et al. Emerging concepts in sporadic cerebral amyloid angiopathy. Brain 2017; 140: 1829–1850. - PMC - PubMed
    1. Knudsen KA, Rosand J, Karluk D, et al. Clinical diagnosis of cerebral amyloid angiopathy: validation of the Boston criteria. Neurology 2001; 56: 537–539. - PubMed
    1. Linn J, Halpin A, Demaerel P, et al. Prevalence of superficial siderosis in patients with cerebral amyloid angiopathy. Neurology 2010; 74: 1346–1350. - PMC - PubMed
    1. Malhotra K, Theodorou A, Katsanos AH, et al. Prevalence of clinical and neuroimaging markers in cerebral amyloid angiopathy: a systematic review and meta-analysis. Stroke 2022; 53: 1944–1953. - PubMed
    1. Theodorou A, Palaiodimou L, Papagiannopoulou G, et al. Clinical characteristics, neuroimaging markers, and outcomes in patients with cerebral amyloid angiopathy: a prospective cohort study. J Clin Med 2023; 12: 5591. - PMC - PubMed

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