The main aims of this study were to quantify the burden of tau-pathology in an autopsy cohort of clinical cases with cerebral amyloid angiopathy (CAA) and to characterize the presence of perivascular tau (PVT) accumulation and its relationship with CAA.  

CAA and Alzheimer's Disease Neuropathological Changes, such as tau-tangles, often coexist. The role of tau pathology in the pathophysiology of CAA remains to be determined.

Autopsy cases with a neuropathologically confirmed clinical diagnosis of CAA were evaluated. Samples were taken from cortical areas and underwent immunohistochemistry against amyloid-β (Aβ) and phosphorylated tau (At8). Deep-learning based models were created and applied to the samples to quantify 1) density of intraneuronal tau-tangles; 2) percentage area of cortical CAA and Aβ-plaques using the Aiforia® platform; 3) percentage area of total cortical tau-burden, using QuPath. Linear-mixed effects models were applied to assess the association between tau and CAA burden. The presence of dyshoric CAA (flamelike Aβ deposits that radiate into the perivascular neuropil), and PVT (accentuated accumulation of tau around the vessel) were visually identified on Aβ vs. At8-stained sections respectively. Single-vessel analysis was performed to determine whether there was an association between PVT and CAA using Chi-square tests. 

A total of 76 sections in 19 CAA cases (median age-at-death 76 years [64–88]; 7 females) were analyzed. Higher tau-tangles and total tau-burden were observed in the temporal cortex versus the occipital cortex (p=0.05). CAA burden was not associated with tau-tangles or total tau-burden. Dyshoric CAA was observed around at least one vessel in 71 (93.4%) of the sections and PVT in 32 (34%) of the sections. In single-vessel analysis, PVT was significantly associated with both dyshoric CAA (p=0.004) and any CAA (p=0.0005).