Development of new biomarkers that can distinguish neurodegenerative diseases based on the detection method of protein amplification assay

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K07417
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Nagasaki University
• Principal Investigator: Satoh Katsuya 長崎大学, 医歯薬学総合研究科(保健学科), 教授 (70398147)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 神経変性疾患 / QUIC / シヌクレイン / TDP-43 / タウ蛋白

Outline of Final Research Achievements

Neurodegenerative diseases involve progressive neurodegeneration due to abnormal protein accumulation. This study explored diagnostic approaches by developing amplification techniques to detect disease-specific abnormal proteins in patient samples. Quantitative assays measuring pathological α-synuclein in brain/cerebrospinal fluid (synuclein QUIC) and abnormal TDP-43 (TDP-43 QUIC) were successfully established. In parallel, efforts focused on differentiating 3R/4R tau isoforms, key in tauopathies, but discriminating them proved challenging despite using recombinant tau proteins and assessing amyloid formation. While promising for diagnosis, further optimization and validation are needed before clinical implementation of detecting abnormal protein conformers in biofluids. Reliably identifying disease-specific proteinopathies could complement symptom-based and imaging diagnostics.

Free Research Field

神経変性疾患

Academic Significance and Societal Importance of the Research Achievements

従来の症状や画像所見に加え、異常蛋白を検出できればより早期の段階で神経変性疾患を診断できる。早期診断により、症状の進行を遅らせたり、QOLを維持したりできる。又異常蛋白の種類や蓄積レベルを定量評価できれば、個々の疾患の発症メカニズムや病態をより深く理解できる。これは新しい治療法の開発につながる。さらに、異常蛋白をバイオマーカーとして用いれば、新薬の有効性評価が正確になり、有望な治療法の臨床開発が促進される。生体材料からの検査は比較的侵襲が少なく簡便であり、検出法が実用化されれば広く普及する。このように異常蛋白検出技術の確立は神経変性疾患の診断・治療の向上に寄与し、その社会的意義は大きい。