ALS患者CSF中潜在生物学标记物的确定

来源 :世界核心医学期刊文摘(神经病学分册) | 被引量 : 0次 | 上传用户:TNT2000
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Background: The clinical diagnosis of ALS is based entirely on clinical features. Identification of biomarkers for ALS would be important for diagnosis and might also provide clues to pathogenesis. Objective: To determine if there is a specific protein profile in the CSF that distinguishes patients with ALS from those with purely motor peripheral neuropathy (PN) and healthy control subjects. Methods: CSF obtained from patients with ALS, disease controls (patients with other neurologic disorders), and normal controls were analyzed using the surface- enhanced laser desorption/ ionization time- of- flight mass spectrometry proteomics technique. Biomarker sensitivity and specificity was calculated with receiver operating characteristic curve methodology. ALS biomarkers were purified and sequence identified by mass spectrometry- directed peptide sequencing. Results: In initial proteomic discovery studies, three protein species (4.8- , 6.7- , and 13.4- kDa) that were significantly lower in concentration in the CSF from patients with ALS (n = 36) than in normal controls (n = 21) were identified. A combination of three protein species (the “ three- protein” model) correctly identified patients with ALS with 95% accuracy, 91% sensitivity, and 97% specificity from the controls. Independent validation studies using separate cohorts of ALS (n = 13), healthy control (n = 25), and PN (n = 7) subjects confirmed the ability of the three CSF protein species to separate patients with ALS from other diseases. Protein sequence analysis identified the 13.4- kDa protein species as cystatin C and the 4.8- kDa protein species as a peptic fragment of the neurosecretory protein VGF. Conclusion: Additional application of a “ three- protein” biomarker model to current diagnostic criteria may provide an objective biomarker pattern to help identify patients with ALS. Background: The clinical diagnosis of ALS is based entirely on clinical features. Identification of biomarkers for ALS would be important for diagnosis and might also provide clues to pathogenesis. Objective: To determine if there is a specific protein profile in the CSF that distinguishes patients with ALS from those with purely motor peripheral neuropathy (PN) and healthy control subjects. Methods: CSF obtained from patients with ALS, disease controls (patients with other neurologic disorders), and normal controls were analyzed using the surface-enhanced laser desorption / ionization time - of-flight mass spectrometry proteomics technique. Biomarker sensitivity and specificity was calculated with receiver operating characteristic curve methodology. ALS biomarkers were purified and sequence identified by mass spectrometry-directed peptide sequencing. -, 6.7-, and 13.4-kDa) that were significantly lower in c A combination of three protein species (the “three-protein” model) correctly identified patients with ALS with 95% accuracy, n = 36, Independent validation studies using separate cohorts of ALS (n = 13), healthy control (n = 25), and PN (n = 7) subjects confirmed the ability of the three CSF protein species to separate patients with ALS from other diseases. Protein sequence analysis identified the 13.4-kDa protein species as cystatin C and the 4.8-kDa protein species as a peptic fragment of the neurosecretory protein VGF. Conclusion: Additional application of a “three-protein ”Biomarker model to current diagnostic criteria may provide an objective biomarker pattern to help identify patients with ALS.
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