Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease.
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.
Zhang
Jing
J
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.
Goodlett
Dave R
DR
Quinn
Joseph F
JF
Peskind
Elaine
E
Kaye
Jeffrey A
JA
Zhou
Yong
Y
Pan
Catherine
C
Yi
Eugene
E
Eng
Jimmy
J
Wang
Qin
Q
Aebersold
Ruedi H
RH
Montine
Thomas J
TJ
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
D015415:Biomarkers; D020543:Proteome