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

• Published in: Frontiers in aging neuroscience Vol. 14; p. 783996
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 14.02.2022; Frontiers Media S.A
• Subjects: Alzheimer's disease; Alzheimer’s dementia (AD); Automation; Biobanks; Biomarkers; Boston criteria; Cerebral amyloid angiopathy; cerebral amyloid angiopathy (CAA); Cerebrospinal fluid; cerebrospinal fluid (CSF); Clinical trials; Dementia; Diagnostic tests; high-precision electro-chemiluminescence immunoassay (ECLIA); Hospitals; Laboratories; Meta-analysis; Nervous system; Neurodegenerative diseases; Neurological disorders; Neuroscience; Patients; Tau protein; cerebral amyloid angiopathy (CAA); Boston criteria; cerebrospinal fluid (CSF); high-precision electro-chemiluminescence immunoassay (ECLIA); Alzheimer’s dementia (AD)
• ISSN: 1663-4365; 1663-4365
• DOI: 10.3389/fnagi.2022.783996

To 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. Beta-amyloid 1-40 (Aβ40), beta-amyloid 1-42 (Aβ42), total tau (t-tau), and phosphorylated tau 181 (p-tau ) 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. In 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-tau (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-tau (AUC 0.71). P-tau (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. 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.