Alzheimer-specific alterations of 4 repeat tau for pathological diagnosis and its clinical application for CSF testing

2021 Fiscal Year Final Research Report

• Project/Area Number: 17H03555
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Tokyo Medical and Dental University (2018-2021); Tokyo Metropolitan Institute of Medical Science (2017)
• Principal Investigator: Uchihara Toshiki 東京医科歯科大学, 大学院医歯学総合研究科, 特任教授 (10223570)
• Co-Investigator(Kenkyū-buntansha): 吉田 眞理 愛知医科大学, 付置研究所, 特命研究教授 (60288545)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: 4リピートタウ / 脱アミド化 / アルツハイマー病

Outline of Final Research Achievements

This project is aimed at establishing ELISA quantification of CSF tau protein D279-4R, that is abundant in AD but not in PSP brains. This difference is now patented as a potential marker to distinguish AD and PSP. However, trials to establish an IgG clone with exclusive affinity to D279-4R were not successful but yielded a clone with affinity to both D279-4R and N279-4R. We are now characterizing this clone in comparison with RD4 with exclusive affinity to N279-4R. It is possible that this comparison will provide a tool to distinguish AD and PSP based on their difference in 4R tau species.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

髄液中のタウは脳内に沈着したタウを反映しているが、現在実用化されている髄液中のタウ定量法はタウ全体を測定するので疾患の質を区別できていない。我々が同定したD279-4Rタウはアルツハイマー病脳に豊富だがPSP脳では検出されない。ADに特異的なD279-4Rタウを髄液中に検出できれば、ADタウ病変が脳に存在することが示唆され、従来とは異なる画期的診断法となると期待される。さらにこの抗体を免疫療法に用いるとAD病変選択的な親和性が期待され、特異度の高い治療法につながる可能性がある。