Sporadic CJD histotyping by means of activated microglia profiling

The differences in lesion profile among sporadic (s) CJD subtypes to date has been mainly characterized in terms of distribution of histopathological lesions and amount of PrPSc, although strain related differences in microglial response have also been suggested. We studied the relationship between PrPSc deposition, microglial cell activation, and histopathological lesions in 8 brain regions from 37 sCJD cases of the most common subtypes. The regional profile of microglial activation, evaluated by means of HLA-D immunohistochemistry, showed significant differences among MM1, VV2, and MV2 sCJD subtypes, and overall significantly correlated with the lesion profile (spongiform changes and astrogliosis) and the regional distribution of PrPSc in typical cases. The overlap of the three profiles, however, was less evident in cases of long duration, particularly in the MM1 subtype. Finally, MM1 cases showed similarhistopathological scores but significant lower levels of PrPSc accumulation compared to both VV2 and MV2 subjects. The present results suggest that HLA profiling represents a valuable tool for sCJD subtype classification. The lack of a significant confounding effect of neuronal loss, particularly in long duration cases, represents an advantage of this approach.