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 signi...

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Published in:Journal of neuropathology and experimental neurology 2009-08, Vol.68 (8), p.892-901
Main Authors: Faucheux, Baptiste A, Privat, Nicolas, Brandel, Jean-Philippe, Sazdovitch, Véronique, Laplanche, Jean-Louis, Maurage, Claude-Alain, Hauw, Jean-Jacques, Haïk, Stéphane
Format: Article
Language:English
Subjects:
Astrocytes - metabolism
Astrocytes - pathology
Biological and medical sciences
Cerebellum - pathology
Creutzfeldt-Jakob Syndrome - metabolism
Creutzfeldt-Jakob Syndrome - pathology
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
Humans
Medical sciences
Neurology
Neurons - metabolism
Neurons - pathology
Prions - metabolism
PrPSc Proteins - genetics
PrPSc Proteins - metabolism
Statistics as Topic
Synapses - metabolism
Synapses - pathology
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Summary: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-μm-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.
ISSN:0022-3069
1554-6578
DOI:10.1097/NEN.0b013e3181af7f23