Comparative proteomic profiling of cerebrospinal fluid between living and post mortem ALS and control subjects

Document Type

Article

Abstract

Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), lack definitive diagnostic tests or biomarkers of disease progression. Most studies that investigate protein abnormalities in ALS have used biofluids such as blood or cerebrospinal fluid (CSF), while some have used post mortem tissue or CSF samples. Since ALS disease progression and post mortem effects probably induce significant alterations to protein modifications or proteolysis, we directly examined the CSF proteome from ALS subjects at various lengths of time from symptom onset and at autopsy by mass spectrometry based proteomics. CSF was also obtained from both healthy age-matched control subjects and at autopsy from healthy and Alzheimer's disease (AD) controls. We identified significant differences in the CSF proteome between living and post mortem ALS subjects, as well as living and post mortem control subjects. We also noted differences in the CSF proteome of ALS subjects that have exhibited symptoms for varying lengths of time and between ALS and AD subjects at end-stage of disease. This is the first study describing differences in the CSF proteome from post mortem and living ALS subjects using a mass spectrometric approach. These differences highlight the importance of utilizing CSF from living ALS subjects near the time of symptom onset for the identification of early protein biomarkers, although some protein alterations that occur early in the disease process are maintained throughout the course of disease and in post mortem samples.

Keywords

Biomarkers, Cerebrospinal fluid, Mass spectrometry, Proteomics

Publication Date

12-4-2007

Publication Title

Amyotrophic Lateral Sclerosis

ISSN

17482968

E-ISSN

1471180X

Volume

8

Issue

6

First Page

373

Last Page

379

PubMed ID

17852009

Digital Object Identifier (DOI)

10.1080/17482960701549681

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