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 Aβ42/40, 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 Aβ42/40, p-tau-181, NfL and GFAP were quantified using Simoa and Aβ42/40 was also independently quantified using immunoprecipitation liquid chromatography mass-spectrometry (IPMS).

RESULTS 45 participants with CAA and 47 healthy controls had available plasma. Aβ42/40 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 Aβ42/40 (Simoa), p-tau-181, and NfL resulted in an AUC of 0.90 (95% CI: 0.80, 0.95).

DISCUSSION Plasma Aβ42/40, p-tau-181 and NfL differ in those with CAA and together can discriminate CAA from healthy controls.

RTM, SS, JGC, AEB, CRM, MG, KN, NN, JV, MDH RC, and CLW do not have any perceived or actual conflicts of interest relevant to this work. KMK is employed by C2N Diagnostics. SEB declares the following Contract Research GE Healthcare, Genentech, Optina, Roche, Eli Lilly, Eisa/Biogen Idec, NovoNordisk, Lilly Avid. Payments made to Institution and no personal investigator fees taken including Eli Lilly. Consulting Fees from Roche, Biogen, Eli Lilly, NovoNordisk and Eisai. Payments made to me. Honoraria, Biogen, Roche Models of Care Analysis in Canada and Eisai MRI Workshop. Payments made to me. EES has previously served on a steering committee (unpaid) for Alnylam Pharmaceuticals and on advisory boards (unpaid) for Eisai and Eli Lilly.

This study was funded by: Canadian Institutes for Health Research, Alzheimer's Society of Canada and the Hotchkiss Brain Institute, University of Calgary

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The Functional Assessment of Vascular Reactivity in Small Vessel Disease-II (FAVR-II) Study is a prospective cohort study approved by the University of Calgary and University of Alberta Research Ethics Boards (REB). Written informed consent was provided by all participants.

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