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 Simoa and Aβ 42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS). RESULTS 45 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 AUC of 0.90 (95% CI: 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.