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Abstract
Creutzfeldt-Jakob disease (CJD) is a heterogenic neurodegenerative disorder associated with abnormal post-translational processing of cellular prion protein (PrPc). CJD displays distinctive clinical and pathological features which correlate with the genotype at the codon 129 (methionine or valine: M or V respectively) in the prion protein gene and with size of the protease-resistant core of the abnormal prion protein PrPsc (type 1: 20/21 kDa and type 2: 19 kDa). MM1 and VV2 are the most common sporadic CJD (sCJD) subtypes. PrP mRNA expression levels in the frontal cortex and cerebellum are reduced in sCJD in a form subtype-dependent. Total PrP protein levels and PrPsc levels in the frontal cortex and cerebellum accumulate differentially in sCJD MM1 and sCJD VV2 with no relation between PrPsc deposition and spongiform degeneration and neuron loss, but with microgliosis, and IL6 and TNF-α response. In the CSF, reduced PrPc, the only form present in this compartment, occurs in sCJD MM1 and VV2. PrP mRNA expression is also reduced in the frontal cortex in advanced stages of Alzheimer disease, Lewy body disease, progressive supranuclear palsy, and frontotemporal lobe degeneration, but PrPc levels in brain varies from one disease to another. Reduced PrPc levels in CSF correlate with PrP mRNA expression in brain, which in turn reflects severity of degeneration in sCJD.
Disclosure of Potential Conflicts of Interest
No potential conflicts of interest were disclosed.
Acknowledgments
This study was funded by the Seventh Framework Program of the European Commission DEVELAGE project, the European Union Joint Program DEMTEST, the Spanish Ministry of Health, Instituto Carlos III: FIS PI1100968, and CIBERNED project BESAD-P. We are grateful for the support for previous studies in the context of the BrainNet Europe II, LSHM-CT-2004-503039. Supply of brain samples from the Biobank of Hospital Clinic-IDIBAPS is acknowledged. We thank all brain donors and relatives for generous brain donation for research, as well as referring physicians; Dr Judith Navarro and Carina Antiga for their support in the Brain Donor Program; Rosa Ribera, Sara Charif, Abel Muñoz, Leire Etxarri, Esteban González and Jesús González for their technical support; and T Yohannan for editorial assistance. E Gelpí is partly funded by the Spanish “Ministerio de Economía y Competitividad, Subprograma Técnicos de Apoyo, 2011.”