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Subtype-Specific Synaptic Proteome Alterations in Sporadic Creutzfeldt-Jakob Disease

Article type: Research Article

Authors: Gawinecka, Joannaa; 1 | Nowak, Martina; 1 | Carimalo, Juliea | Cardone, Francod | Asif, Abdul R.b | Wemheuer, Wiebke M.c | Schulz-Schaeffer, Walter J.c | Pocchiari, Mauriziod | Zerr, Ingaa; *

Affiliations: [a] National Reference Center for TSE, Medical Center Georg-August University, Goettingen, Germany | [b] Department of Clinical Chemistry, Medical Center Georg-August University, Goettingen, Germany | [c] Department of Neuropathology, Medical Center Georg-August University, Goettingen, Germany | [d] Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Rome, Italy

Correspondence: [*] Correspondence to: Inga Zerr, Prion Research Group, National Reference Center for TSE, Department of Neurology, University Medical School, Georg-August University, Robert-Koch Street. 40, 37075 Göttingen, Germany. Tel.: +49 (0)551/39 6636; Fax: +49 (0)551/39 7020; E-mail: [email protected].

Note: [1] These authors contributed equally to the work.

Keywords: Creutzfeldt-Jakob disease, 2D fluorescence difference gel electrophoresis (2D DIGE), proteomics, sCJD, synapse, synaptic dysfunction

DOI: 10.3233/JAD-130455

Journal: Journal of Alzheimer's Disease, vol. 37, no. 1, pp. 51-61, 2013

Accepted 25 April 2013
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Published: 20 August 2013
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Supplementary Materials:

Table S1.

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.

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