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

This 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.

The spatial patterns of prion protein deposits in cases of variant Creutzfeldt-Jakob disease

The spatial patterns of the prion protein (PrP) deposits were studied in immunostained sections of areas of the cerebral cortex, hippocampus, dentate gyrus, and the molecular layer of the cerebellum in 11 cases of variant Creutzfeldt-Jakob disease (vCJD). Clustering of PrP deposits, with a regular distribution of the clusters parallel to the tissue boundary, was the most common spatial pattern observed. Two morphological types of PrP deposit were recognised, those consisting of a condensed core (florid deposits) and those deposits lacking a condensed core (non-florid deposits). The florid and non-florid PrP deposits exhibited a different profile of spatial patterns. First, the florid deposits exhibited a regularly distributed pattern of clusters more frequently than the non-florid deposits. Second, the florid deposits formed larger clusters (greater than1,600 µm in diameter) less frequently than the non-florid deposits. In the areas of the cerebral cortex that exhibited a regular distribution of PrP deposit clusters, the cluster size of the deposits approximated that of the groups of cells of the cortico-cortical pathway origin in only 12% of analyses. No significant differences in the frequency of the different types of spatial pattern were observed in different brain regions, or in the cerebral cortex between the upper and lower laminae. It was concluded that the spatial patterns of the PrP deposits in the cerebral cortex in vCJD are unlikely to reflect the degeneration of the cortico-cortical pathways as has been reported in sporadic CJD (sCJD). In addition, different factors could be involved in the development of the deposits with and without a condensed core.

Quantification of vacuolation ('spongiform change'), surviving neurones and prion protein deposition in eleven cases of variant Creutzfeldt-Jakob disease

Vacuolation ('spongiform change') and prion protein (PrP) deposition were quantified in the cerebral cortex, hippocampus, dentate gyrus and molecular layer of the cerebellum in 11 cases of variant Creutzfeldt-Jakob disease (vCJD). The density of vacuoles was greater in the cerebral cortex compared to the hippocampus, dentate gyrus and cerebellum. Within the cortex, vacuole density was significantly greater in the occipital compared to the temporal lobe and the density of surviving neurones was greatest in the occipital lobe. The density of the non-florid PrP plaques was greater in the cerebellum compared to the other brain areas. There were significantly more florid-type PrP plaques in the cerebral cortex compared to the hippocampus and the molecular layer of the cerebellum. No significant correlations were observed between the densities of the vacuoles and the PrP plaques. The densities of vacuoles in the parietal cortex and the non-florid plaques in the frontal cortex were positively correlated with the density of surviving neurones. The densities of the florid and the non-florid plaques were positively correlated in the parietal cortex, occipital cortex, inferior temporal gyrus and dentate gyrus. The data suggest: (i) vacuolation throughout the cerebral cortex, especially in the occipital lobe, but less evident in the hippocampus and molecular layer of the cerebellum; (ii) the non-florid plaques are more common than the florid plaques and predominate in the molecular layer of the cerebellum; and (iii) either the florid plaques develop from the non-florid plaques or both types are morphological variants resulting from the same degenerative process.

Quantification of the vacuolation (spongiform change) and prion protein deposition in 11 patients with sporadic Creutzfeldt-Jakob disease

The vacuolation (spongiform change) and prion protein (PrP) deposition were quantified in the cerebral cortex, hippocampus and cerebellum of 11 patients with sporadic Creutzfeldt-Jakob disease (CJD). The density of the vacuolation, averaged over patients, was greatest in the occipital cortex and cerebellum and least in the dentate gyrus. The degree of PrP deposition was similar in the different cortical areas and in the cerebellum but significantly lower in the hippocampus and absent in the dentate gyrus. There were no significant differences in the extent of the vacuolation and PrP deposition in the upper and lower cortical laminae. Vacuolation and PrP deposition in the upper cortex were both positively correlated with corresponding levels in the lower cortex. In addition, in the parietal cortex and parahippocampal gyrus, the density of the vacuolation was positively correlated with the level of PrP deposition but no such correlations were observed in the remaining areas studied. This quantitative study suggested that: (1) the pathological changes were most severe in the occipital cortex and cerebellum, while the hippocampus was least affected, (2) the pathological changes affect the upper and lower cortical laminae, and (3) the degree of correlation between the density of the vacuolation and PrP deposition may be dependent on brain region.

Spatial pattern of prion protein deposits in patients with sporadic Creutzfeldt–Jakob disease

The spatial pattern of the prion protein (PrP) deposits was studied in the cerebral cortex and cerebellum in 10 patients with sporadic Creutzfeldt–Jakob disease (CJD). In all patients the PrP deposits were aggregated into clusters and, in 90% of cortical areas and in 50% of cerebellar sections, the clusters exhibited a regular periodicity parallel to the tissue boundary; a spatial pattern also exhibited by ß-amyloid (Aß) deposits in Alzheimer's disease (AD). In the cerebral cortex, the incidence of regular clustering of the PrP deposits was similar in the upper and lower cortical laminae. The sizes of the PrP clusters in the upper and lower cortex were uncorrelated. No significant differences in mean cluster size of the PrP deposits were observed between brain regions. The size, location and distribution of the PrP deposit clusters suggest that PrP deposition occurs in relation to specific anatomical pathways and supports the hypothesis that prion pathology spreads through the brain via such pathways. In addition, the data suggest that there are similarities in the pathogenesis of extracellular protein deposits in prion disease and in AD.