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

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

JOURNAL=Frontiers in Aging Neuroscience

VOLUME=Volume 14 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/aging-neuroscience/articles/10.3389/fnagi.2022.783996

DOI=10.3389/fnagi.2022.783996

ISSN=1663-4365

ABSTRACT=Background: To evaluate the diagnostic accuracy of CSF biomarkers in patients with probable cerebral amyloid angiopathy (CAA) according to the Modified Boston criteria in a retrospective multicentric cohort.
Methods: Aß40, Aß42, t-tau, and 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 Aß42/40 ratio to estimate diagnostic parameters. A meta-analysis of all amenable published studies was conducted.
Results: In our data Aß42/40 (AUC 0.88) discriminated best between CAA and controls while Aß40 did not perform well (AUC 0.63). Differentiating between CAA and AD, p-tau181 (AUC 0.75) discriminated best in this study while Aß40 (AUC 0.58) and Aß42 (AUC 0.54) provided no discrimination. 
In the meta-analysis, Aß42/40 (AUC 0.90) showed the best discrimination between CAA and controls followed by t-tau (AUC 0.79), Aß40 (AUC 0.76), and p-tau181 (AUC 0.71). p-tau181 (AUC 0.76), Aß40 (AUC 0.73), and t-tau (AUC 0.71) differentiated comparably between AD and CAA while Aß42 (AUC 0.54) did not. In agreement with studies examining AD biomarkers, Aß42/40 discriminated excellently between AD and controls (AUC 0.92-0.96) in this study as well as the meta-analysis.
Conclusions: The 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.