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Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrP Sc ) deposition in sporadic Creutzfeldt–Jakob disease supports a pathogenic role for small PrP Sc deposits common to the various molecular subtypes
Author(s) -
Faucheux B. A.,
Morain E.,
Diouron V.,
Brandel J.P.,
Salomon D.,
Sazdovitch V.,
Privat N.,
Laplanche J.L.,
Hauw J.J.,
Haïk S.
Publication year - 2011
Publication title -
neuropathology and applied neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.538
H-Index - 95
eISSN - 1365-2990
pISSN - 0305-1846
DOI - 10.1111/j.1365-2990.2011.01179.x
Subject(s) - prnp , cerebellum , biology , pathology , pathogenesis , prion protein , creutzfeldt jakob syndrome , granule (geology) , immunohistochemistry , disease , immunology , neuroscience , medicine , paleontology
B. A. Faucheux, E. Morain, V. Diouron, J.‐P. Brandel, D. Salomon, V. Sazdovitch, N. Privat, J.‐L. Laplanche, J.‐J. Hauw and S. Haïk (2011) Neuropathology and Applied Neurobiology 37, 500–512 Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrP Sc ) deposition in sporadic Creutzfeldt–Jakob disease supports a pathogenic role for small PrP Sc deposits common to the various molecular subtypesAims: Neuronal death is a major neuropathological hallmark in prion diseases. The association between the accumulation of the disease‐related prion protein (PrP Sc ) and neuronal loss varies within the wide spectrum of prion diseases and their experimental models. In this study, we investigated the relationships between neuronal loss and PrP Sc deposition in the cerebellum from cases of the six subtypes of sporadic Creutzfeldt–Jakob disease (sCJD; n = 100) that can be determined according to the M129V polymorphism of the human prion protein gene ( PRNP ) and PrP Sc molecular types. Methods: The numerical density of neurones was estimated with a computer‐assisted image analysis system and the accumulation of PrP Sc deposits was scored. Results: The scores of PrP Sc immunoreactive deposits of the punctate type (synaptic type) were correlated with neurone counts – the higher the score the higher the neuronal loss – in all sCJD subtypes. Large 5‐ to 50‐µm‐wide deposits (focal type) were found in sCJD‐MV2 and sCJD‐VV2 subtypes, and occasionally in a few cases of the other studied groups. By contrast, the highest scores for 5‐ to 50‐µm‐wide deposits observed in sCJD‐MV2 subtype were not associated with higher neuronal loss. In addition, these scores were inversely correlated with neuronal counts in the sCJD‐VV2 subtype. Conclusions: These results support a putative pathogenic role for small PrP Sc deposits common to the various sCJD subtypes. Furthermore, the observation of a lower loss of neurones associated with PrP Sc type‐2 large deposits is consistent with a possible ‘protective’ role of aggregated deposits in both sCJD‐MV2 and sCJD‐VV2 subtypes.