Plasma Amyloid Beta and Tau Associations with Cerebral Amyloid Angiopathy Presence and Severity

OBJECTIVE: The aim was to determine whether plasma amyloid beta (Aβ) Aβ37, Aβ40, Aβ42, and p-tau217 differ in cerebral amyloid angiopathy (CAA) from controls and associate with specific magnetic resonance imaging (MRI) markers of CAA. METHODS: Single center hospital-based study (Massachusetts General Hospital) enrolling patients with probable or definite CAA per Boston 2.0 criteria among consecutive individuals presenting with spontaneous intracerebral hemorrhage (ICH) and non-acute ICH related symptoms. Control participants were identified among individuals 55 years or older without history of ICH attending outpatient clinics in the same catchment area and time as the CAA cases. Primary outcome tested whether plasma Aβ37, Aβ40, Aβ42, and p-tau217 differ between patients with CAA and controls. Secondary outcome evaluated the correlation with the severity of selected CAA neuroradiological hallmarks on brain MRI scans obtained within 1 year of sample collection. RESULTS: A total of 186 patients with CAA (mean age, 71.2 ± 8.3 years; males, 107 58%) and 401 controls (mean age, 73.9 ± 8.3 years; males, 211 53%) were included in the study. CAA cases had lower Aβ40 (β = -0.60, 95% CI = -0.80 to -0.40, P < 0.001), Aβ42 (β = -0.48, 95% CI = -0.70 to -0.27, P < 0.001), and higher p-tau217 (β = 0.73, 95 %CI = 0.54 to 0.91, P < 0.001) concentrations compared to controls. Aβ40 was the only fragment reduced independent of ptau217 levels. Within the CAA group, biomarkers were associated with both hemorrhagic (reduced Aβ42 with cortical superficial siderosis) and non-hemorrhagic (reduced Aβ40 and Aβ42 with enlarged perivascular spaces in centrum semiovale, reduced Aβ37 and increased p-tau217 with white matter hyperintensities) MRI hallmarks of CAA. INTERPRETATION: Plasma Aβ40, Aβ42, and p-tau217 differ between CAA patients and controls and are informative on CAA severity as inferred from brain MRI markers. ANN NEUROL 2026.