Biomarkers of Multiple System Atrophy Focusing on Oligodendroglia

• Project/Area Number: 18K15442
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Niigata University
• Principal Investigator: Tokutake Takayoshi 新潟大学, 医歯学総合病院, 助教 (00707838)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Project Status: Completed (Fiscal Year 2021)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 多系統萎縮症 / バイオマーカー / 脳脊髄液 / オリゴデンドログリア / αシヌクレイン

Outline of Final Research Achievements

Multiple system atrophy (MSA) is a progressive neurodegenerative disorder. Clinical diagnosis of MSA could be challenging particularly in early stage, because of the phenotypic heterogeneity. In this study, we aimed to evaluate diagnostic value of CSF biomarkers and characterize its association with clinical parameters. We quantified CSF biomarkers including α-synuclein (α-syn), β-Amyloid42 (Aβ42), total tau (t-tau) and phosphorylated tau (p-tau) and NG2 in MSA patients. Clinical parameters including motor symptoms, nonmotor symptoms were assessed in association with CSF biomarkers. We found that CSF α-syn, Aβ42, and p-tau were significantly lower in MSA patients than in controls. We demonstrated that soluble NG2 is significantly elevated in CSF of MSA patients. The levels of CSF Aβ42 were significantly correlated with cognitive impairment in MSA. This study highlighted that CSF biomarkers may help distinguish MSA patients from control subjects.

Academic Significance and Societal Importance of the Research Achievements

多系統萎縮症の病態研究が進み，国内外で病態機序に即した疾患修飾薬の開発がすすめられている．疾患修飾薬の開発が進んだ場合，神経細胞の脱落が進んだ不可逆な状態では，薬剤の効果は限定的と考えられ，治療介入が可能な発症早期の診断が重要となってくる．多系統萎縮症は多様な臨床表現型を呈し，発症早期の診断は難しいケースが少なくないことから，早期診断に有用なバイオマーカーが求められている．また多系統萎縮症患者の症状進行速度は患者間で差が大きく，発症後の進行を予測するバイオマーカーも重要性が増している．本研究は多系統萎縮症の早期診断，進行予測に寄与しうると考えられる．

Research Products

• [Presentation] 多系統萎縮症における脳脊髄液中NG2と臨床症状の検討 (2021)
  • Author(s): 徳武孝允
  • Organizer: 第62回日本神経学会学術集会
• [Presentation] 多系統萎縮症における認知機能障害と脳脊髄液バイオマーカーの検討 (2021)
  • Author(s): 徳武孝允
  • Organizer: 第40回日本認知症学会学術大会
• [Presentation] Analysis of CSF alpha-synuclein, amyloid-beta and tau in multiple system atrophy (2020)
  • Author(s): Takayoshi Tokutake， Kensaku Kasuga，Tamao Tsukie， Yo Higuchi， Takayoshi Shimohata，Osamu Onodera，Takeshi Ikeuchi
  • Organizer: 7th International Congress of Multiple System Atrophy
  • Int'l Joint Research
• [Presentation] 多系統萎縮症における脳脊髄液中NG2とα-シヌクレインの検討 (2020)
  • Author(s): 徳武孝允、春日健作、月江珠緒、樋口陽、下畑享良、小野寺理、池内健
  • Organizer: 第61回日本神経学会学術大会
• [Presentation] 多系統萎縮症における脳脊髄液中NG2と認知機能の検討 (2020)
  • Author(s): 徳武孝允、春日健作、月江珠緒、樋口陽、下畑享良、小野寺理、池内健
  • Organizer: 第39回日本認知症学会学術集会
• [Presentation] 多系統萎縮症における脳脊髄液バイオマーカーの検討 (2019)
  • Author(s): 徳武孝允
  • Organizer: 第60回日本神経学会学術大会
• [Presentation] 多系統萎縮症における脳脊髄液バイオマーカーと認知機能の検討 (2019)
  • Author(s): 徳武孝允
  • Organizer: 第38回日本認知症学会学術集会
• [Presentation] 多系統萎縮症における認知症関連・脳脊髄液バイオマーカーの検討 (2018)
  • Author(s): 徳武孝允
  • Organizer: 第37回認知症学会学術集会