Quantitative proteomics of cerebrospinal fluid from patients with Alzheimer disease

Article type: Research Article

Authors: Zhang, Jing^a | Goodlett, Dave R.^b | Quinn, Joseph F.^c | Peskind, Elaine^{d; e} | Kaye, Jeffrey A.^c | Zhou, Yong^a | Pan, Catherine^a | Yi, Eugene^f | Eng, Jimmy^f | Wang, Qin^a | Aebersold, Ruedi H.^f | Montine, Thomas J.^{a; c; *}

Affiliations: [a] Departments of Pathology, University of Washington School of Medicine, Seattle, WA, USA | [b] Departments of Medicinal Chemistry, University of Washington School of Medicine, Seattle, WA, USA | [c] Department of Neurology, Oregon Health Science University, Portland, OR, USA | [d] Department of Psychiatry and Behavioral Sciences, University of Washington School of Medicine, Seattle, WA, USA | [e] Mental Illness Research, Education, and Clinical Center, VA Puget Sound Health Care System, Seattle, WA, USA | [f] Mental Illness Research, Institute of Systems Biology, Seattle, WA, USA

Correspondence: [*] Corresponding author: Thomas J. Montine, M.D., Ph.D., Division of Neuropathology, University of Washington School of Medicine, Box 359791, Harborview Medical Center, Seattle, WA 98104, USA. Tel.: +1 206 731 4106; Fax: +1 206 341 5349; E-mail: [email protected].

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 ≥ 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.

Keywords: Alzheimer disease, biomarkers, cerebrospinal fluid, proteomics

DOI: 10.3233/JAD-2005-7205

Journal: Journal of Alzheimer's Disease, vol. 7, no. 2, pp. 125-133, 2005