Detection of biomarkers with a multiplex quantitative proteomic platform in cerebrospinal fluid of patients with neurodegenerative disorders

Article type: Research Article

Authors: Abdi, Fadi^{a; **} | Quinn, Joseph F.^{b; **} | Jankovic, Joseph^c | McIntosh, Martin^d | Leverenz, James B.^e | Peskind, Elaine^e | Nixon, Randy^b | Nutt, John^b | Chung, Katherine^b | Zabetian, Cyrus^e | Samii, Ali^e | Lin, Melanie^a | Hattan, Stephen^a | Pan, Catherine^e | Wang, Yan^e | Jin, Jinghua^e | Zhu, David^e | Li, G. Jane^e | Liu, Yan^d | Waichunas, Dana^b | Montine, Thomas J.^e | Zhang, Jing^{e; *}

Affiliations: [a] Applied Biosystems, Framingham, MA, USA | [b] Oregon Health and Science University, Portland, OR, USA | [c] Baylor College of Medicine, Houston, TX, USA | [d] Fred Hutchison Cancer Research Center, Seattle, WA, USA | [e] University of Washington School of Medicine, Seattle, WA, USA

Correspondence: [*] Corresponding author: Jing Zhang, MD, PhD, Division of Neuropathology, University of Washington School of Medicine, Box 359635 Harborview Medical Center, Seattle, WA 98104, USA. Tel.: +1 206 341 5245; Fax: +1 206 341 5249; E-mail: zhangj@u.washington.edu.

Note: [**] Authors who have contributed equally.

Abstract: Biomarkers are needed to assist in the diagnosis and medical management of various neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy body (DLB). We have employed a multiplex quantitative proteomics method, iTRAQ (isobaric Tagging for Relative and Absolute protein Quantification), in conjunction with multidimensional chromatography, followed by tandem mass spectrometry (MS/MS), to simultaneously measure relative changes in the proteome of cerebrospinal fluid (CSF) obtained from patients with AD, PD, and DLB compared to healthy controls. The diagnosis of AD and DLB was confirmed by autopsy, whereas the diagnosis of PD was based on clinical criteria. The proteomic findings showed quantitative changes in AD, PD, and DLB as compared to controls; among more than 1,500 identified CSF proteins, 136, 72, and 101 of the proteins displayed quantitative changes unique to AD, PD, and DLB, respectively. Eight unique proteins were confirmed by Western blot analysis, and the sensitivity at 95% specificity was calculated for each marker alone and in combination. Several panels of unique makers were capable of distinguishing AD, PD and DLB patients from each other as well as from controls with high sensitivity at 95% specificity. Although these preliminary findings must be validated in a larger and different population of patients, they suggest that a roster of proteins may be generated and developed into specific biomarkers that could eventually assist in clinical diagnosis and monitoring disease progression of AD, PD and DLB.

Keywords: Alzheimer disease, biomarkers, Parkinson disease, proteomics

DOI: 10.3233/JAD-2006-9309

Journal: Journal of Alzheimer's Disease, vol. 9, no. 3, pp. 293-348, 2006