title: Quantitative proteomic analysis of age-related changes in human cerebrospinal fluid.
abstract: Identification of cerebrospinal fluid (CSF) biomarkers of the common age-related neurodegenerative diseases would be of great value to clinicians because of the difficulties in differential diagnoses of these diseases in clinical practice. Proteins are one class of potential biomarkers currently under investigation in the hope that different ensembles of proteins will aid in the diagnosis of these diseases, as well as in the assessment of progression and response to therapy. However, before undertaking a rational approach to CSF protein biomarkers of age-related neurodegeneration, we must first systematically identify CSF proteins and determine whether their levels change with normal aging. In this study, we used a powerful shotgun proteomic method, two-dimensional microcapillary liquid chromatography electrospray ionization tandem mass spectrometry, to identify proteins in human CSF. Additionally, using pooled CSF samples, we quantitatively compared the CSF proteome of younger adults with that of older adults using isotope-coded affinity tags (ICAT). From these studies we identified more than 300 proteins in CSF and found that there were 30 proteins with >20% change in concentrations between older and younger individuals. Finally, we validated changes in concentration for two of these proteins using Western blots in CSF from a separate set of individuals. These data not only expand substantially our current knowledge regarding human CSF proteins, but also supply the necessary information to appropriately interpret protein biomarkers of age-related neurodegenerative diseases.
authors.affiliation: Division of Neuropathology, University of Washington School of Medicine, Box 359635, Harborview Medical Center, Seattle, WA 98104, USA. zhangj@u.washington.edu
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: David R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Elaine R
authors.initials: ER
authors.lastname: Peskind
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Catherine
authors.initials: C
authors.lastname: Pan
authors.forename: Eugene
authors.initials: E
authors.lastname: Yi
authors.forename: Jimmy
authors.initials: J
authors.lastname: Eng
authors.forename: Ruedi H
authors.initials: RH
authors.lastname: Aebersold
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid*; D015153:Blotting, Western / Q000379:methods; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid* / Q000145:classification; D002853:Chromatography, Liquid / Q000379:methods; D030562:Databases, Protein; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics / Q000379:methods*; D015203:Reproducibility of Results
chemical_list: D002556:Cerebrospinal Fluid Proteins; D020543:Proteome