Classic β-Amyloid Deposits Cluster Around Large Diameter Blood Vessels Rather than Capillaries in Sporadic Alzheimers Disease

Richard   A.   Armstrong

Abstract

Various hypotheses could explain the relationship between β-amyloid (Aβ) deposition and the vasculature in Alzheimers disease (AD). Amyloid deposition may reduce capillary density, affect endothelial cells of blood vessels, result in diffusion from blood vessels, or interfere with the perivascular clearance mechanism. Hence, the spatial pattern of the classic (cored) type of Aβ deposit was studied in the upper laminae (I,II/III) of the superior frontal gyrus in nine cases of sporadic AD (SAD). Sections were immunostained with antibodies against Aβ and with collagen IV to study the relationships between the spatial distribution of the classic deposits and the blood vessel profiles. Both the classic deposits and blood vessel profiles were distributed in clusters. In all cases, there was a positive spatial correlation between the clusters of the classic deposits and the larger diameter ( > 10 μm) blood vessel profiles and especially the vertically penetrating arterioles. In only 1 case, was there a significant spatial correlation between the clusters of the classic deposits and the smaller diameter ( < 10 μm) capillaries. There were no negative correlations between the density of Aβ deposits and the smaller diameter capillaries. In 9/11 cases, the clusters of the classic deposits were significantly larger than those of the clusters of the larger blood vessel profiles. In addition, the density of the classic deposits declined as a negative exponential function with distance from a vertically penetrating arteriole. These results suggest that the classic Aβ deposits cluster around the larger blood vessels in the upper laminae of the frontal cortex. This aggregation could result from diffusion of proteins from blood vessels or from overloading the system of perivascular clearance from the brain.

Keywords: Clustering, frontal cortex, blood vessels, diffusion, perivascular clearance, negative exponential model, spatial correlation

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