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Abstract
Objective To perform a meta-analysis of 4 core CSF biomarkers (β-amyloid [Aβ]42, Aβ40, total tau [t-tau], and phosphorylated tau [p-tau]) to assess which of these are most altered in sporadic cerebral amyloid angiopathy (CAA).
Methods We systematically searched PubMed for eligible studies reporting data on CSF biomarkers reflecting amyloid precursor protein metabolism (Aβ42, Aβ40), 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.
Results Three 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 Aβ42 (RoM 0.49, 95% confidence interval [CI] 0.38–0.64, p < 0.003), Aβ40 (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 Aβ40 (RoM 0.76, 95% CI 0.69–0.83, p < 0.0001), but not Aβ42 (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.
Conclusion Specific CSF patterns of Aβ42, Aβ40, t-tau, and p-tau might serve as molecular biomarkers of CAA, but analyses in larger CAA cohorts are needed.
Glossary
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- CAA=
- cerebral amyloid angiopathy;
- CI=
- confidence interval;
- ICH=
- intracerebral hemorrhage;
- p-tau=
- phosphorylated tau;
- RoM=
- ratio of means;
- t-tau=
- total tau
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
CME Course: NPub.org/cmelist
- Received June 29, 2017.
- Accepted in final form November 28, 2017.
- © 2018 American Academy of Neurology
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- Core CSF biomarker profile in cerebral amyloid angiopathy: A meta-analysis
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