Abstract Background and aims Cerebral amyloid angiopathy (CAA) is characterized by amyloid-β accumulation in leptomeningeal and cortical vessels and is a leading cause of intracerebral hemorrhage. Additionally, CAA is associated with white matter (WM) injury, which arises remotely from vascular Aβ-deposition and is linked to cognitive decline. However, WM microvascular pathology—particularly arteriolosclerosis—has not been systematically examined in the context of CAA. This study aims to assess the severity of WM arteriolosclerosis and its interaction with CAA pathology in an autopsy cohort. Methods Arteriolosclerosis was semi-quantitatively assessed in histological sections stained with Luxol blue with HE of 26 definite CAA autopsy cases (76.6 years ± 7.4). Additionally, an AI-based algorithm was developed using Aiforia® to quantify the arteriolar sclerotic index (SI) as a measure of arteriolosclerosis severity (Fig. 1). Finally, 3-dimensional histological reconstruction (ie, scanning at micro-CT voxel size:12mm3, serial sectioning, alignment to CT-scans) was performed on two brain samples (1.6x 2.0x 0.3 cm) to perform single-vessel analysis. Results Higher subcortical arteriolosclerosis burden was locally associated with greater cortical CAA %area (β = 0.095, SE = 0.048, P = 0.051). The AI model reliably quantified SI (Area error(arterial wall width): 0.63%; Area error(lumen): 0.07%). Single-vessel analysis showed that 66% of arterioles with CAA in their cortical portion presented moderate to severe arteriolosclerosis in their WM portion (Fig. 2). Conclusions Arteriolosclerosis severity is regionally associated with CAA burden. Furthermore, CAA and arteriolosclerosis often co-exist within different portions of the same perforating cortical vessels. These results suggest a pathophysiological contribution of arteriolosclerosis to CAA. Conflict of interest All authors: nothing to disclose. Figure 1 - belongs to Methods Figure 2 - belongs to Results
Rotta et al. (Fri,) studied this question.