Extent of Tau and Its Cognitive Implications in Patients With Cerebral Amyloid Angiopathy Without Cognitive Impairment

BACKGROUND AND OBJECTIVES: Despite a well-established amyloid-tau neurodegeneration cascade in Alzheimer disease (AD), the extent and mechanistic relevance of tau pathology in cerebral amyloid angiopathy (CAA), a disease of vascular amyloid deposition, remain unclear. Focusing on patients with CAA without cognitive impairment to minimize concurrent AD pathology, we hypothesized that tau extent would be greater in patients with CAA than in healthy controls (HCs), largely attributable to amyloid burden, but it would not be associated with CAA-related imaging markers or cognitive scores in CAA. METHODS: F-flortaucipir (FTP)-PET for tau. Tau extent was estimated based on PET-Braak staging from cortical FTP uptake and categorized into earlier (Braak 0, I-II) vs later (Braak III-VI) PET-Braak stages. Cognitive scores obtained in CAA were standardized z-scores for memory, processing speed, and executive function. Multivariable regression models tested the association of tau extent with (1) CAA diagnosis and amyloid load in the whole cohort [CAA and HC] and (2) amyloid load, CAA-related imaging markers, and cognitive scores within the CAA cohort. RESULTS: > 0.2). DISCUSSION: Our results suggest that tau extent is mainly driven by age and vascular amyloid among patients with CAA and that tau extent is not related to CAA-related imaging markers or cognitive scores. These findings further support the view that tau does not affect CAA-specific disease mechanisms among patients with CAA without cognitive impairment.