Comparative proteomics of cerebrospinal fluid in neuropathologically-confirmed Alzheimer's disease and non-demented elderly subjects.
OBJECTIVE
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-beta 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.


CONCLUSIONS
These results suggest that multi-factor proteomic pattern analysis of the CSF may provide a means to diagnose and assess AD.
The Longtine Center for Molecular Biology and Genetics, Sun Health Research Institute, Sun City, Arizona 85351, USA.
Eduardo M
EM
Castaño
Alex E
AE
Roher
Chera L
CL
Esh
Tyler A
TA
Kokjohn
Thomas
T
Beach
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism*; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000032:analysis / Q000134:cerebrospinal fluid; D015415:Biomarkers / Q000032:analysis / Q000134:cerebrospinal fluid; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002402:Cathepsin D / Q000032:analysis / Q000134:cerebrospinal fluid; D015180:Electrophoresis, Gel, Two-Dimensional; D005136:Eye Proteins / Q000032:analysis / Q000134:cerebrospinal fluid; D005260:Female; D006466:Hemopexin / Q000032:analysis / Q000134:cerebrospinal fluid; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D009414:Nerve Growth Factors / Q000032:analysis / Q000134:cerebrospinal fluid; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000134:cerebrospinal fluid*; D011228:Prealbumin / Q000032:analysis / Q000134:cerebrospinal fluid; D011237:Predictive Value of Tests; D040901:Proteomics / Q000379:methods; D012016:Reference Values; D015843:Serpins / Q000032:analysis / Q000134:cerebrospinal fluid; D000099174:Pigment Epithelium-Derived Factor
D016229:Amyloid beta-Peptides; D016632:Apolipoprotein A-I; D015415:Biomarkers; D002402:Cathepsin D; D005136:Eye Proteins; D006466:Hemopexin; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D011228:Prealbumin; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor