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Profiling of miRNAs in cerebrospinal fluid from patients with multifocal motor neuropathy and amyotrophic lateral sclerosis

  • P3-312
  • 大久保 卓哉 / Takuya Ohkubo:1 町田 明 / Akira Machida:1,11 茂櫛 薫 / Kaoru Mogushi:2 松尾 秀徳 / Hidenori Matsuo:3 角田 篤信 / Atsushi Tsunoda:4 前原 健寿 / Taketoshi Maehara:5 能登 祐一 / Yu-ichi Noto:6 清水 俊夫 / Toshio Shimizu:7 桑原 聡 / Satoshi Kuwabara:8 神田 隆 / Takashi Kanda:9 小坂 展慶 / Nobuyoshi Kosaka:10 落谷 孝弘 / Takahiro Ochiya:10 横田 隆徳 / Takanori Yokota:1 
  • 1:医科歯科大院・医・脳神経病態 / Dept Neurol & Neurosci, Univ of Tokyo Med & Dent, Japan 2:順天堂・医・ゲノム再生 / Div Genome Res, CBRR, Univ of Juntendo, Tokyo, Japan 3:長崎川棚医療セ・神内 / NHO, Nagasaki Kawatana Med Cent, Nagasaki, Japan 4:医科歯科大院・医・耳鼻 / Dept Otolaryngol, Univ of Tokyo Med & Dent, Tokyo, Japan 5:医科歯科大院・医・脳外 / Dept Neurosurg, Univ of Tokyo Med & Dent, Tokyo, Japan 6:京府医大院・医・神内 / Dept Neurol, Kyoto Prefectural Univ of Med, Kyoto, Japan 7:都立神経病院・神内 / Dept Neurol, Tokyo Metro Neurol Hosp, Tokyo, Japan 8:千葉大院・医・神内 / Dept Neurol, Univ of Chiba, Chiba, Japan 9:山口大院・医・神内 / Dept Neurol and Clin Neurosci, Univ of Yamaguchi, Ube, Japan 10:国立がん研セ・分子細 / Div Mol Ce 11:Dept Neurol, Tsuchiura Kyodo General Hosp, Ibaraki, Japan 

Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder by progressive loss of motor neurons. Multifocal motor neuropathy (MMN) is an acquired immune-mediated demyelinating neuropathy with slowly progressive weakness, which is treatable and sometimes mistaken for ALS because of similar clinical features. There is no established diagnostic or prognostic biomarker for distinguishing MMN from ALS. We evaluated whether miRNAs are differentially regulated in the CSF from MMN and ALS, compared with CSF from normal controls. ALS (n=23), MMN (n=13) and normal controls (n=10) were included in 3D-GENE miRNAs array study (Toray). After collecting CSF by standard lumbar puncture techniques, cells were removed by centrifugation, and RNA was extracted by miRNeasy mini kit (Qiagen). Microarray analysis was performed according to the manufacturer's instructions. The miRNA array identified 4 down regulated miRNAs and 14 upregulated miRNAs in the CSF of ALS patients relative to that of normal controls. In addition, 11 miRNAs were detected only in ALS patients (P<0.05). By using a combination of 5 miRNAs detected only in the CSF of ALS patients, we could best differentiate ALS patients from normal controls with a sensitivity of 73.9%. Then, 34 miRNAs were significantly decreased in MMN compared with ALS. The combination of two miRNAs among them (AUC>0.95) could differentiate ALS from MMN with extremely high sensitivity of 92.3% and specificity of 95.7%. These two miRNAs in CSF might be good biomarker for discriminating between MMN and ALS.

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