The relative abundance of APOE and Aβ1-42 associated with abnormal prion protein differs between Creutzfeldt-Jakob disease subtypes

Roger A. Moore, Young Pyo Choi, Mark Head, James Ironside, Robert Farris, Diane Ritchie, Gianluigi Zanusso, Suzette A. Priola

Research output: Contribution to journalArticlepeer-review

Abstract

Aggregated and protease-resistant mammalian prion protein (PrPSc) is the primary protein component of infectious prions. Enriched PrPSc preparations are often used to study the mechanisms underlying prion disease. However, most enrichment procedures are relatively nonspecific and tend to yield significant amounts of non-PrPSc components, including various proteins that could confound functional and structural studies. It is thus important to identify
these proteins and assess their potential relevance to prion pathogenesis. Following proteinase K treatment and phosphotungstic acid precipitation of brain homogenate, we have used mass spectrometry to analyze the protein content of PrPSc isolated from prion-infected mice, multiple cases of sporadic Creutzfeldt-Jakob disease (sCJD), and human growth hormone associated cases
of iatrogenic CJD (iCJD). Creatine kinase was the primary protein contaminant in all PrPSc samples while many of the other proteins identified were also found in non-CJD controls, suggesting that they are not CJD specific. Interestingly, the Alzheimer’s disease associated peptide amyloid β 1-42 (Aβ1-42) was identified in the majority of the sCJD cases as well as non-CJD age-matched controls while apoliprotein E was found in greater abundance in the sCJD cases. By contrast, while some of the iCJD cases showed evidence of higher molecular weight Aβ oligomers, monomeric Aβ1-42 peptide was not detected by immunoblot and only one case had significant levels of apolipoprotein E. Our data are consistent with the age-associated deposition of Aβ1-42 in older sporadic CJD and non-CJD patients and suggest that both apolipoprotein E and Aβ1-42 abundance can differ depending upon the type of CJD.
Original languageEnglish
JournalJournal Of Proteome Research
Early online date1 Oct 2016
DOIs
Publication statusE-pub ahead of print - 1 Oct 2016

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