Identification of ALS-related brain networks and development of a diagnostic/monitoring system

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K12670
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 90130:Medical systems-related
• Research Institution: Juntendo University (2021-2022); The University of Tokushima (2020)
• Principal Investigator: Sako Wataru 順天堂大学, 医学部, 准教授 (60581155)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 筋萎縮性側索硬化症 / バイオマーカー / MRI / fMRI / MRS / 一次運動野 / 補足運動野 / 感覚運動ネットワーク

Outline of Final Research Achievements

The objective diagnosis and monitoring system is important to perform clinical trials for amyotrophic lateral sclerosis (ALS). We hypothesized that brain networks-related alterations in MRI, MR spectroscopy, and protein biomarkers could contribute to building a new diagnostic and monitoring system. Increased glutamate and decreased N-acetyl aspartate concentrations were reported in the supplementary motor cortex, and serum neurofilament light chain concentrations were found to be excellent for ALS diagnosis even in the early stages. MRI can detect reduced volume of the primary motor cortex in cases that do not meet diagnostic criteria of ALS but actually have ALS, and is expected to help the diagnosis. We also found that atrophy of the primary motor cortex was associated with hyperactivity of the sensory-motor network.

Free Research Field

医用システム関連

Academic Significance and Societal Importance of the Research Achievements

筋萎縮性側索硬化症 (ALS)における補足運動野のグルタミン酸/N-アセチルアスパラギン酸 (NAA)比の上昇は、ALSの神経興奮毒性仮説に矛盾しないグルタミン酸の上昇、神経細胞減少と関連するNAA減少を統合したバイオマーカーとなりうる可能性がある。進行期だけではなく、早期のALSでも血清神経フィラメント軽鎖濃度減少が診断に有用なことも証明でき、早期診断のバイオマーカーとしてのエビデンス構築にも寄与できた。一次運動野容量の減少、全灰白質容量の経時的減少も報告でき、上記報告と併せALS診断・モニタリングシステム構築へ近づくことができた。