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

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 (A beta 40), beta-amyloid 1-42 (A beta 42), total tau (t-tau), and phosphorylated tau 181 (p-tau(181)) 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 A beta 42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted. ResultsIn our data A beta 42/40 (AUC 0.88) discriminated best between CAA and controls while A beta 40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau(181) (AUC 0.75) discriminated best in this study while A beta 40 (AUC 0.58) and A beta 42 (AUC 0.54) provided no discrimination. In the meta-analysis, A beta 42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), A beta 40 (AUC 0.76), and p-tau(181) (AUC 0.71). P-tau(181) (AUC 0.76), A beta 40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while A beta 42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, A beta 42/40 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 > similar to 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.