Abstract TP078: Utility of Plasma Phosphorylated Tau 217 in Cerebral Amyloid Angiopathy and Its Association with Cognitive Function

Introduction: Plasma phosphorylated tau 217 (p-tau 217) is a biomarker of β-amyloid pathology; however, its utility in patients with imaging suggestive of cerebral amyloid angiopathy (CAA) is unclear. We hypothesized that cases classified as probable CAA would have higher p-tau 217 levels than those with possible or no CAA, and that levels would be associated with major neurocognitive disorder (MND). Methods: This is a retrospective analysis of prospectively collected patients seen in an outpatient stroke clinic, who were referred for cerebrovascular disease with a primary complaint of subjective cognitive impairment. Brain magnetic resonance imaging scans were reviewed by two neurologists to classify CAA according to the Boston Criteria 2.0 (inter-rater reliability score kappa = 0.65, p < 0.001). Serum p-tau 217 levels were collected and classified as negative if ≤0.185 pg/ml, intermediate if 0.186-0.324 pg/ml, and positive if ≥0.325 pg/ml. Results: Of 40 patients included in this analysis, the mean age was 75±10 years, and 53% were female. There were 26 (65%) patients classified as probable CAA. Among the 36 (90%) patients with p-tau 217 testing, mean p-tau 217 levels were significantly higher in patients with probable CAA compared to patients with possible or no CAA (0.377±0.241 vs 0.172±0.111, p = 0.001). In a subset of 23 (58%) patients who had neuropsychological evaluations, patients with probable CAA were more likely to have MND than patients with possible or no CAA (27% vs 13% respectively, p=0.15) and were more cognitively impaired based on the Montreal Cognitive Assessment (mean score of 19.2±6.6 vs 23.0±3.7 respectively, p=0.08). Conclusions: Probable CAA patients demonstrated significantly higher plasma p-tau 217 levels and a trend towards a higher frequency of major neurocognitive disorder, supporting p-tau 217 as a potential biomarker for both amyloid pathology and cognitive decline in CAA patients.