title: Subtype-specific synaptic proteome alterations in sporadic Creutzfeldt-Jakob disease.
abstract: Sporadic Creutzfeldt-Jakob disease (sCJD) is characterized by wide clinical and pathological variability, which is mainly influenced by the conformation of the misfolded prion protein (PrPSc) and by methionine and valine polymorphism at codon 129 of the gene encoding PrP. This heterogeneity likely implies differences in the molecular cascades that lead to the development of certain disease phenotypes. Here, we investigated synaptic proteome patterns in two most common sCJD subtypes (MM1 and VV2) using 2D DIGE and mass spectrometry. We found that 23 distinct proteins were differentially expressed in at least one sCJD subtype when compared to age-matched controls. The majority of these proteins displayed significant subtype-specific alterations, with only up-regulated glial fibrillary acidic protein and down-regulated spectrin alpha chain in both sCJD subtypes. Differentially expressed proteins found in this study are mainly involved in synaptic structure and activity, mitochondrial function, or calcium metabolism. Moreover, several of them have been already linked to the pathophysiological processes occurring in Alzheimer's disease.
authors.affiliation: National Reference Center for TSE, Medical Center Georg-August University, Goettingen, Germany.
authors.forename: Joanna
authors.initials: J
authors.lastname: Gawinecka
authors.forename: Martin
authors.initials: M
authors.lastname: Nowak
authors.forename: Julie
authors.initials: J
authors.lastname: Carimalo
authors.forename: Franco
authors.initials: F
authors.lastname: Cardone
authors.forename: Abdul R
authors.initials: AR
authors.lastname: Asif
authors.forename: Wiebke M
authors.initials: WM
authors.lastname: Wemheuer
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Schulz-Schaeffer
authors.forename: Maurizio
authors.initials: M
authors.lastname: Pocchiari
authors.forename: Inga
authors.initials: I
authors.lastname: Zerr
mesh_terms: D000368:Aged; D007562:Creutzfeldt-Jakob Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
chemical_list: D020543:Proteome