Cerebral tau pathology in cerebral amyloid angiopathy

Abstract

Tau, a hallmark of Alzheimer’s disease, is poorly characterized in cerebral amyloid angiopathy. We aimed to assess the clinico-radiological correlations between tau PET scans and cerebral amyloid angiopathy. We assessed cerebral amyloid and hyperphosphorylated tau in patients with probable cerebral amyloid angiopathy (n=31) and hypertensive small vessel disease (n=27) using 11C- Pittsburgh compound B and 18F-T807 PET. Multivariable regression models were employed to assess radio-clinical features related to cerebral tau pathology in cerebral amyloid angiopathy. Cerebral amyloid angiopathy exhibited a higher cerebral tau burden in the inferior temporal lobe (1.25 [1.17‒1.42] vs. 1.08 [1.05‒1.22], P<0.001) and all Braak stage regions of interest (P<0.05) than hypertensive small vessel disease, though the differences were attenuated after age adjustment. Cerebral tau pathology was significantly associated with cerebral amyloid angiopathy-related vascular markers, including cortical superficial siderosis (β=0.12, 95% confidence interval 0.04‒0.21) and cerebral amyloid angiopathy score (β=0.12, 95% confidence interval 0.03‒0.21) after adjustment for age, ApoE4 status and whole cortex amyloid load. Tau pathology correlated significantly with cognitive score (Spearman’s ρ=-0.56, P=0.001) and hippocampal volume (-0.49, P=0.007), even after adjustment. In conclusion, tau pathology is more frequent in sporadic cerebral amyloid angiopathy than hypertensive small vessel disease. Cerebral amyloid angiopathy-related vascular pathologies, especially cortical superficial siderosis, are potential markers of cerebral tau pathology suggestive of concomitant Alzheimer’s disease.