Frontiers in Aging Neuroscience (Feb 2022)

Cerebrospinal Fluid Biomarkers in Cerebral Amyloid Angiopathy: New Data and Quantitative Meta-Analysis

  • Nils G. Margraf,
  • Ulf Jensen-Kondering,
  • Ulf Jensen-Kondering,
  • Caroline Weiler,
  • Frank Leypoldt,
  • Frank Leypoldt,
  • Walter Maetzler,
  • Sarah Philippen,
  • Thorsten Bartsch,
  • Charlotte Flüh,
  • Christoph Röcken,
  • Bettina Möller,
  • Georg Royl,
  • Alexander Neumann,
  • Norbert Brüggemann,
  • Norbert Brüggemann,
  • Benjamin Roeben,
  • Benjamin Roeben,
  • Claudia Schulte,
  • Claudia Schulte,
  • Benjamin Bender,
  • Daniela Berg,
  • Daniela Berg,
  • Gregor Kuhlenbäumer

DOI
https://doi.org/10.3389/fnagi.2022.783996
Journal volume & issue
Vol. 14

Abstract

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BackgroundTo evaluate the diagnostic accuracy of cerebrospinal fluid (CSF) biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the modified Boston criteria in a retrospective multicentric cohort.MethodsBeta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau181) were measured in 31 patients with probable CAA, 28 patients with Alzheimer’s disease (AD), and 30 controls. Receiver-operating characteristics (ROC) analyses were performed for the measured parameters as well as the Aβ42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted.ResultsIn our data Aβ42/40 (AUC 0.88) discriminated best between CAA and controls while Aβ40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aβ40 (AUC 0.58) and Aβ42 (AUC 0.54) provided no discrimination. In the meta-analysis, Aβ42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aβ40 (AUC 0.76), and p-tau181 (AUC 0.71). P-tau181 (AUC 0.76), Aβ40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aβ42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aβ42/40 discriminated excellently between AD and controls (AUC 0.92–0.96) in this study as well as the meta-analysis.ConclusionThe analyzed parameters differentiate between controls and CAA with clinically useful accuracy (AUC > ∼0.85) but not between CAA and AD. Since there is a neuropathological, clinical and diagnostic continuum between CAA and AD, other diagnostic markers, e.g., novel CSF biomarkers or other parameters might be more successful.

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