title: Comparative proteomic profiling of cerebrospinal fluid between living and post mortem ALS and control subjects.
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.
authors.affiliation: Neurogenetics Branch, National Institute of Neurological Disorders and Stroke, National Institute of Health, Bethesda, MD, USA.
authors.forename: Srikanth
authors.initials: S
authors.lastname: Ranganathan
authors.forename: Georgina C B
authors.initials: GC
authors.lastname: Nicholl
authors.forename: Sarah
authors.initials: S
authors.lastname: Henry
authors.forename: Fran
authors.initials: F
authors.lastname: Lutka
authors.forename: Ramasri
authors.initials: R
authors.lastname: Sathanoori
authors.forename: David
authors.initials: D
authors.lastname: Lacomis
authors.forename: Robert
authors.initials: R
authors.lastname: Bowser
mesh_terms: D000328:Adult; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid* / Q000235:genetics* / Q000473:pathology; D015415:Biomarkers / Q000134:cerebrospinal fluid; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011180:Postmortem Changes; D020543:Proteome / Q000096:biosynthesis* / Q000235:genetics*; D040901:Proteomics / Q000379:methods*
chemical_list: D015415:Biomarkers; D020543:Proteome