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

摘要

ObjectiveTo perform a meta-analysis of 4 core CSF biomarkers (-amyloid [A]42, A40, total tau [t-tau], and phosphorylated tau [p-tau]) to assess which of these are most altered in sporadic cerebral amyloid angiopathy (CAA).MethodsWe systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting amyloid precursor protein metabolism (A42, A40), 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.ResultsThree 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 A42 (RoM 0.49, 95% confidence interval [CI] 0.38-0.64, p 0.003), A40 (RoM 0.70, 95% CI 0.63-0.78, p 0.0001), and t-tau (RoM 1.54, 95% CI 1.15-2.07, p = 0.004); p-tau was marginal (RoM 1.24, 95% CI 0.99-1.54, p = 0.062). Differentiation between CAA and AD was strong for CSF A40 (RoM 0.76, 95% CI 0.69-0.83, p 0.0001), but not A42 (RoM 1.00; 95% CI 0.81-1.23, p = 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, p 0.0001) and 0.60 (95% CI 0.50-0.71, p 0.0001), respectively.ConclusionSpecific CSF patterns of A42, A40, t-tau, and p-tau might serve as molecular biomarkers of CAA, but analyses in larger CAA cohorts are needed.