title: Quantification of surviving cerebellar granule neurones and abnormal prion protein (PrPSc) deposition in sporadic Creutzfeldt-Jakob disease supports a pathogenic role for small PrPSc deposits common to the various molecular subtypes.
abstract: OBJECTIVE
  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.
authors: Assistance Publique - Hôpitaux de Paris (AP-HP), Laboratoire de Neuropathologie, Hôpital de la Salpêtrière, 47 boulevard de l'Hôpital Centre de Recherche de l'Institut du Cerveau et de la Moelle, INSERM UMRS975, CNRS UMR7225, Paris, France. baptiste.faucheux@upmc.fr
authors: B A
authors: BA
authors: Faucheux
authors: E
authors: E
authors: Morain
authors: V
authors: V
authors: Diouron
authors: J-P
authors: JP
authors: Brandel
authors: D
authors: D
authors: Salomon
authors: V
authors: V
authors: Sazdovitch
authors: N
authors: N
authors: Privat
authors: J-L
authors: JL
authors: Laplanche
authors: J-J
authors: JJ
authors: Hauw
authors: S
authors: S
authors: Haïk
mesh_terms: D002452:Cell Count; D016923:Cell Death / Q000502:physiology; D002531:Cerebellum / Q000378:metabolism / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D015151:Immunoblotting; D007150:Immunohistochemistry; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018620:PrPSc Proteins / Q000378:metabolism*
chemical_list: D018620:PrPSc Proteins