Abstract Body: Introduction: Previous studies have shown an association between vascular disease and Alzheimer’s disease, but there are few studies have considered a relationship between brain arterial remodeling and biomarkers of Alzheimer's disease. Our study aims to find the association between specific arterial characteristics in brain arterial remodeling and Alzheimer's pathology.
Method: We analyzed 132 brain autopsy cases from the Brain Arterial Remodeling Study (BARS), a collection of brains from multiple brain banks in the United States and abroad. Brain sections were obtained systematically by each brain bank, and the anatomical location was harmonized across the banks. The brain slides were stained with LH&E to measure the lumen and wall thickness of the pial, CSF-floating small arteries, parenchymal arteries, and arterioles. Then lumen area, wall thickness, lumen-to-wall ratio (LWR), and wall proportion (which serves as a measure of vessel stenosis) were calculated. We used immunohistochemistry to stain for beta-amyloid, phospho-tau, and Iba1, a measure of microglia. Each stained slide was processed automatically using Visiopharm (version 2021.12) by color thresholding and pattern detection to quantify the number of amyloid plaques and microglial (Iba1+ cells) per 100 µm² and the percentage of tissue area stained positive by phospho-tau, and the number of microglial cells per 100 µm².
Results: Overall, a thicker arterial wall was associated with a greater area of tau staining and a lower lumen-to-wall ratio (suggestive of inward remodeling) was associated with a higher number of microglial cells (table 1). There was a statistical interaction between measures of arterial remodeling by anatomical location (pial vs. parenchymal, P<0.01) and amyloid measures. Stratifying by arterial anatomical location, however, demonstrated that parenchymal arteries with large lumen (B=0.12 ±0.03 per µm², P<0.001) and thicker arterial wall (B=1.10 ± 0.18 per µm², P<0.001) had a higher number of amyloid plaques per 100 µm².
Conclusion: Brain arteries immediately supplying the brain and their parenchymal offsprings related to measures of tau phosphorylation and neuroinflammation. Parenchymal arteries and arterioles that are dilated proportional to their wall thickness also relate to a greater load of amyloid deposition. Further investigation is needed to clarify these relationships.