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
