Loss of cerebellar granule neurons is associated with punctate but not with large focal deposits of prion protein in Creutzfeldt-Jakob disease.
Whether aggregates of prion protein (PrP) reflect neurotoxicity or are neuroprotective in prion diseases is unclear. To address this question, we performed a clinicopathologic study of cerebellar granular neurons in 100 patients affected with sporadic Creutzfeldt-Jakob disease (CJD). There was significant loss of these neurons in the subset of cases with Val/Val genotype at PRNP Codon 129 and Molecular Isotype 2 of abnormal PrP (sporadic CJD-VV2) (n=32) compared with both the other CJD subtypes and to controls. Pathological PrP deposits of the punctate-type (synaptic-type) in this subgroup correlated with neuronal loss and proliferation of astrocytes and microglia. By contrast, the numbers of large deposits (5- to 50-microm-diameter) and numbers of amyloid plaques did not correlate with neuronal loss. These findings are consistent with the view that large aggregates may protect neurons by sequestering neurotoxic PrP oligomers, whereas punctate deposits may indicate the location of neuronal death processes in CJD.
Faucheux
Baptiste A
BA
Assistance Publique-Hôpitaux de Paris, Laboratoire de Neuropathologie R. Escourolle, Hôpital de la Salpêtrière, Institut Fédératif de Recherche des Neurosciences de la Pitié-Salpêtrière, Paris, France.
Privat
Nicolas
N
Brandel
Jean-Philippe
JP
Sazdovitch
Véronique
V
Laplanche
Jean-Louis
JL
Maurage
Claude-Alain
CA
Hauw
Jean-Jacques
JJ
Haïk
Stéphane
S
D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002531:Cerebellum / Q000473:pathology*; D007562:Creutzfeldt-Jakob Syndrome / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D018620:PrPSc Proteins / Q000235:genetics / Q000378:metabolism; D011328:Prions / Q000378:metabolism*; D013223:Statistics as Topic; D013569:Synapses / Q000378:metabolism / Q000473:pathology
D018620:PrPSc Proteins; D011328:Prions