Plasma biomarkers distinguish Boston Criteria 2.0 cerebral amyloid angiopathy from healthy controls

INTRODUCTION: Cerebral amyloid angiopathy (CAA) is characterized by the deposition of beta-amyloid (Aβ) in small vessels leading to hemorrhagic stroke and dementia. This study examined whether plasma Aβ_42/40, phosphorylated-tau (p-tau), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) differ in CAA and their potential to discriminate Boston Criteria 2.0 probable CAA from healthy controls. METHODS: Plasma Aβ_42/40, p-tau-181, NfL, and GFAP were quantified using single molecule array (Simoa) and Aβ_42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS). RESULTS: Forty-five participants with CAA and 47 healthy controls had available plasma. Aβ_42/40 ratios were significantly lower in CAA than healthy controls. While p-tau-181 and NfL were elevated in CAA, GFAP was similar. A combination of Aβ_42/40 (Simoa), p-tau-181, and NfL resulted in an area under the curve of 0.90 (95% confidence interval: 0.80, 0.95). DISCUSSION: Plasma Aβ_42/40, p-tau-181, and NfL differ in those with CAA and together can discriminate CAA from healthy controls. Highlights: Participants with CAA had reduced plasma Aβ_42/40 ratios compared to controls. Plasma p-tau-181 and NfL concentrations are elevated in CAA compared to controls. Plasma GFAP was similar in CAA and controls. Together, plasma Aβ_42/40, p-tau-181, and NfL had excellent discriminability for CAA.