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...
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| Published in | Journal of neurochemistry Vol. 95; no. 5; pp. 1461 - 1471 |
|---|---|
| Main Authors | , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Oxford, UK
Blackwell Science Ltd
01.12.2005
Blackwell Blackwell Publishing Ltd |
| Subjects | |
| Online Access | Get full text |
| ISSN | 0022-3042 1471-4159 |
| DOI | 10.1111/j.1471-4159.2005.03478.x |
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| Abstract | 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. |
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| AbstractList | 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.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. 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. 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. 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. [PUBLICATION ABSTRACT] |
| Author | Brown, Robert H. Gopalakrishnan, Vanathi Newhall, Kristyn Cudkowicz, Merit E. Williams, Eric Urbinelli, Leo Ganchev, Philip Ranganathan, Srikanth Lacomis, David Bowser, Robert |
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| Keywords | 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 |
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| Snippet | Amyotrophic lateral sclerosis (ALS) is characterized by degeneration of motor neurons. We tested the hypothesis that proteomic analysis will identify protein... |
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| SubjectTerms | 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 |
| Title | Proteomic profiling of cerebrospinal fluid identifies biomarkers for amyotrophic lateral sclerosis |
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