title: Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease.
abstract: Biomarkers to assist in the diagnosis and medical management of Alzheimer disease (AD) are a pressing need. We have employed a proteomic approach, microcapillary liquid chromatography mass spectrometry of proteins labeled with isotope-coded affinity tags (ICAT), to quantify relative changes in the proteome of human cerebrospinal fluid (CSF) obtained from the lumbar cistern. Using CSF from well-characterized AD patients and age-matched controls at 2 different institutions, we quantified protein concentration ratios of 42% of the 390 CSF proteins that we have identified and found differences > or = 20% in over half of them. We confirmed our findings by western blot and validated this approach by quantifying relative levels of amyloid precursor protein and cathepsin B in 17 AD patients and 16 control individuals. Quantitative proteomics of CSF from AD patients compared to age-matched controls, as well as from other neurodegenerative diseases, will allow us to generate a roster of proteins that may serve as specific biomarker panels for AD and other geriatric dementias.
authors.affiliation: Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.forename: Dave R
authors.initials: DR
authors.lastname: Goodlett
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Quinn
authors.forename: Elaine
authors.initials: E
authors.lastname: Peskind
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Kaye
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
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: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Ruedi H
authors.initials: RH
authors.lastname: Aebersold
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Montine
mesh_terms: D000328:Adult; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D015153:Blotting, Western; D002458:Cell Fractionation; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D008297:Male; D008875:Middle Aged; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods
chemical_list: D015415:Biomarkers; D020543:Proteome