臨床神経学

<シンポジウム(3)―11―4>神経変性疾患の病態解明・その病態とバイオマーカーの開発を目指して

パーキンソン病のバイオマーカーの開発を目指して

徳田 隆彦

京都府立医科大学分子脳病態解析学(神経内科併任)〔〒602―8566 京都市上京区梶井町465〕

In Parkinson's disease (PD), its diagnosis, measurement of progression and response to therapeutic intervention currently rely upon clinical observation. However, there remains a critical need for validated biomarkers for PD. Among proteins in cerebrospinal fluid (CSF) there is ample biochemical, pathological, and genetic evidence that the metabolism of α-synuclein (α-syn) plays a crucial role in the pathogenesis of PD. We first reported that PD patients had significantly lower α-syn levels in their CSF than the control groups. We then investigated the levels of α-syn oligomers in CSF using a specific self-developed ELISA. The levels of α-syn oligomers were significantly higher in the PD compared to the controls, with a sensitivity of 75.0% and a specificity of 87.5% for the diagnosis of PD, demonstrating that CSF α-syn oligomers can be a useful biomarker for diagnosis of PD. We have recently developed a proteomic profiling strategy for PD. CSF proteins were purified with C8 magnetic beads, and mass spectra were obtained by mass spectrometry. By building a Support vector machine classifier, PD and multiple system atrophy (MSA) were classified effectively with good cross-validation accuracy. A proteomic pattern classification method can increase the accuracy of clinical diagnosis of PD and MSA.
Full Text of this Article in Japanese PDF (314K)

(臨床神経, 52:1332−1334, 2012)
key words:バイオマーカー,パーキンソン病,α―シヌクレイン,オリゴマー,プロテオミクス

(受付日:2012年5月25日)