Florid prion protein (PrP) plaques in patients with variant Creutzfeldt‐Jakob disease (vCJD) are spatially related to blood vessels

Abstract

SUMMARYThis study tested the hypothesis that variations in the density of the florid prion protein (PrP) plaques in the brain of patients with variant Creutzfeldt-Jakob disease (vCJD) were spatially related to blood vessels. In 81% of areas of the cerebral cortex sampled and in 37% of the remaining areas, which included the hippocampus, dentate gyrus, and cerebellum, there was a positive spatial correlation between the density of the florid plaques and the larger blood vessel profiles. The frequency of the positive spatial correlations was similar in different anatomical areas of the cerebral cortex and in the upper compared with the lower cortical laminae. The data support the hypothesis that the florid plaques cluster around the larger blood vessels in vCJD, the density of associated plaques increasing with vessel size. The development of florid plaques close to blood vessels may be due to factors associated with the blood vessels that enhance the aggregation of PrP to form the dense cores of florid plaques and is unlikely to reflect the haematogenous spread of PrP into the brain.

Measuring the degree of spatial correlation between histological features in thin sections of brain tissue

“…First, a positive association between a pathological lesion and a normal histological feature of the brain suggests that specific anatomical structures may be involved in the formation of the lesion. For example, certain types of PrP deposit in vCJD may be directly related to blood vessels 15 and in AD, diffuse Aβ deposits may be related to neurons 21 . Second, two different lesions may be positively associated because there is a pathogenic link between them, for example in AD there may be a relationship between the development of Aβ deposits and NFT 9 or in CJD, between the vacuolation and PrP deposition 30 .…”

“…In the example described, a significant value of X 2 was observed, indicating that although the value of C 7 is low, there is a statistically significant degree of association between the florid plaques and blood vessels in this tissue. Such an association may imply either that PrP might spread into the brain via the bloodstream, or that factors associated with the blood vessels were important in the formation of the florid plaques 15 …”