Relative Abundance of apoE and Aβ1-42 Associated with Abnormal Prion Protein Differs between Creutzfeldt-Jakob Disease Subtypes.
Aggregated and protease-resistant mammalian prion protein (PrPSc) is the primary protein component of infectious prions. Enriched PrPScpreparations are often used to study the mechanisms that underly prion disease. However, most enrichment procedures are relatively nonspecific and tend to yield significant amounts of non-PrPSccomponents 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 PrPScisolated 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 PrPScsamples, while many of the other proteins identified were also found in non-CJD controls, which suggests 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.
Rocky Mountain Laboratories, National Institute of Allergy & Infectious Disease, National Institutes of Health , Hamilton, Montana 59840, United States.
Roger A
RA
Moore
Laboratory Animal Center, Research Division, Korea Brain Research Institute , Daegu 41068, Republic of Korea.
Young Pyo
YP
Choi
National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh , Edinburgh EH8 9YL, U.K.
Mark W
MW
Head
National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh , Edinburgh EH8 9YL, U.K.
James W
JW
Ironside
Rocky Mountain Laboratories, National Institute of Allergy & Infectious Disease, National Institutes of Health , Hamilton, Montana 59840, United States.
Robert
R
Faris
National CJD Research & Surveillance Unit, Centre for Clinical Brain Sciences, School of Clinical Sciences, University of Edinburgh , Edinburgh EH8 9YL, U.K.
Diane L
DL
Ritchie
Department of Neurosciences, Biomedicine, and Movement Sciences, University of Verona , Verona 37129, Italy.
Gianluigi
G
Zanusso
Rocky Mountain Laboratories, National Institute of Allergy & Infectious Disease, National Institutes of Health , Hamilton, Montana 59840, United States.
Suzette A
SA
Priola
D000328:Adult; D000367:Age Factors; D000368:Aged; D016229:Amyloid beta-Peptides / Q000032:analysis*; D000818:Animals; D001057:Apolipoproteins E / Q000032:analysis*; D007562:Creutzfeldt-Jakob Syndrome / Q000145:classification*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D010446:Peptide Fragments / Q000032:analysis*; D000072002:Prion Proteins / Q000032:analysis* / Q000302:isolation & purification
D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; D000072002:Prion Proteins; C075222:amyloid beta-protein (1-42)
Creutzfeld-Jakob disease; amyloid beta; apolipoprotein E; creatine kinase; mass spectrometry; prion protein; proteomics; transmissible spongiform encephalopathies