Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis.
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.
Ranganathan
Srikanth
S
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
Williams
Eric
E
Ganchev
Philip
P
Gopalakrishnan
Vanathi
V
Lacomis
David
D
Urbinelli
Leo
L
Newhall
Kristyn
K
Cudkowicz
Merit E
ME
Brown
Robert H
RH
Bowser
Robert
R
D000328:Adult; D000465:Algorithms; D000690:Amyotrophic Lateral Sclerosis / Q000134:cerebrospinal fluid*; D015415:Biomarkers / Q000134:cerebrospinal fluid*; D055316:Cystatin C; D015891:Cystatins / Q000134:cerebrospinal fluid; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D018653:Juniperus / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009046:Motor Neurons / Q000378:metabolism; D051859:Neuroendocrine Secretory Protein 7B2 / Q000134:cerebrospinal fluid; D011228:Prealbumin / Q000134:cerebrospinal fluid; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D013116:Spinal Cord / Q000473:pathology
D015415:Biomarkers; C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D051859:Neuroendocrine Secretory Protein 7B2; D011228:Prealbumin; C497678:SCG5 protein, human