Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis

• Published in: Journal of neurochemistry Vol. 95; no. 5; pp. 1461 - 1471
• Main Authors: Ranganathan, Srikanth, Williams, Eric, Ganchev, Philip, Gopalakrishnan, Vanathi, Lacomis, David, Urbinelli, Leo, Newhall, Kristyn, Cudkowicz, Merit E., Brown, Robert H., Bowser, Robert
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.12.2005; Blackwell; Blackwell Publishing Ltd
• Subjects: Adult; Algorithms; Amyotrophic lateral sclerosis; Amyotrophic Lateral Sclerosis - cerebrospinal fluid; Biological and medical sciences; Biomarkers - cerebrospinal fluid; Body fluids; cerebrospinal fluid; Cerebrospinal fluid. Meninges. Spinal cord; Comparative studies; Cystatin C; Cystatins - cerebrospinal fluid; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Female; Humans; Hypotheses; Immunohistochemistry - methods; Juniperus - metabolism; Male; mass spectrometry; Medical sciences; Middle Aged; Motor Neurons - metabolism; Nervous system (semeiology, syndromes); Neuroendocrine Secretory Protein 7B2 - cerebrospinal fluid; Neurology; Prealbumin - cerebrospinal fluid; Proteins; Proteomics; Proteomics - methods; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization - methods; Spinal Cord - pathology; Immunohistochemistry; Nervous system diseases; proteomics; Pathogenesis; Ions; Amyotrophic lateral sclerosis; Motor neuron; Cerebrospinal fluid; Protein; Central nervous system disease; Predictive value; Degenerative disease; Degeneration; Spinal cord disease; Learning algorithm; Mass spectrometry; Algorithm analysis
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2005.03478.x

Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein biomarkers that provide insight into disease pathogenesis and are diagnostically useful. To identify ALS specific biomarkers, we compared the proteomic profile of cerebrospinal fluid (CSF) from ALS and control subjects using surface‐enhanced laser desorption/ionization‐time of flight mass spectrometry (SELDI‐TOF‐MS). We identified 30 mass ion peaks with statistically significant (p < 0.01) differences between control and ALS subjects. Initial analysis with a rule‐learning algorithm yielded biomarker panels with diagnostic predictive value as subsequently assessed using an independent set of coded test subjects. Three biomarkers were identified that are either decreased (transthyretin, cystatin C) or increased (carboxy‐terminal fragment of neuroendocrine protein 7B2) in ALS CSF. We validated the SELDI‐TOF‐MS results for transthyretin and cystatin C by immunoblot and immunohistochemistry using commercially available antibodies. These findings identify a panel of CSF protein biomarkers for ALS.