Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer's disease and non-demented elderly subjects
Source: Neurological Research, Volume 28, Number 2, March 2006 , pp. 155-163(9)
Publisher: Maney Publishing
Abstract:Objectives: Diagnostic tests able to reveal Alzheimer's disease (AD) in living patients before cognitive ability is destroyed are urgently needed. Such tests must distinguish AD from other dementia causes, as well as differentiate subtle changes associated with normal aging from true pathology emergence. A single biomarker offering such diagnostic and prognostic capacities has eluded identification. Therefore, a valuable test for AD is likely to be based on a specific pattern of change in a set of proteins, rather than a single protein.
Methods: We examined pooled cerebrospinal fluid (CSF) samples obtained from neuropathologically-confirmed AD (n=43) and non-demented control subjects (n=43) using 2-dimensional gel electrophoresis (2DE) proteomic methodology to detect differentially expressed proteins. Proteins exhibiting expression level differences between the pools were recovered and identified using matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry.
Results: Five differentially-expressed proteins with potential roles in amyloid- metabolism and vascular and brain physiology [apolipoprotein A-1 (Apo A-1), cathepsin D (CatD), hemopexin (HPX), transthyretin (TTR), and two pigment epithelium-derived factor (PEDF) isoforms] were identified. Apo A-1, CatD and TTR were significantly reduced in the AD pool sample, while HPX and the PEDF isoforms were increased in AD CSF.
Discussion: These results suggest that multi-factor proteomic pattern analysis of the CSF may provide a means to diagnose and assess AD.
Document Type: Research Article
Affiliations: 1: The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, Arizona 85351, USA; Fundacion Instituto Leloir, C1405BWE, Buenos Aires, Argentina, USA 2: The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, Arizona 85351, USA 3: The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, Arizona 85351, USA; Department of Microbiology, Midwestern University, Glendale, Arizona 85308, USA 4: W.H. Civin Laboratory for Neuropathology, Sun Health Research Institute, Sun City, Arizona 85351, USA
Publication date: 2006-03-01
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