Analysis of relationship between beta amyloid accumulation and autophagic pathway

2022 Fiscal Year Final Research Report

• Project/Area Number: 17K08524
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General anatomy (including histology/embryology)
• Research Institution: Tokyo Medical University
• Principal Investigator: Takahashi Reisuke 東京医科大学, 医学部, 准教授 (50453725)
• Co-Investigator(Kenkyū-buntansha): 内原 俊記 東京医科歯科大学, 大学院医歯学総合研究科, 特任教授 (10223570)
• Project Period (FY): 2017-04-01 – 2023-03-31
• Keywords: 認知症 / 神経病理 / アルツハイマー病 / β-アミロイド / オートファジー

Outline of Final Research Achievements

It had previously reported that loss of autophagy was involved in neurodegeneration even in the absence of any mutant proteins. Therefore, it was predicted that autophagy function is lost or attenuated in AD, and intraneuronal accumulation of Aβ could induce dysfunction of autophagy in AD transgenic mouse brain with aging. Employing Tg2576 mouse we observed intraneuronal expression of Beclin 1, autophagic protein, with aging. However, the reduction of intraneuronal Beclin 1 was not observed in Tg2576 mouse brain tissue by immunohistochemical labelling. In contrast, remarkable reduction of intraneuronal Beclin 1 was observed in brain tissue from patients with dementia. These results might be able to conclude that human brain tissue is more available to investigate intraneuronal autophagic dysfunction than mouse tissue.

Free Research Field

医学

Academic Significance and Societal Importance of the Research Achievements

現在の高齢化社会においてADの早期診断法の確立は社会的に極めて重要な課題である。オートファジーの変化に着目したAD早期診断法の確立のためには、ADモデルマウス脳組織よりもヒト脳組織を用いた解析が有効であることが本研究により明らかとなった。このことは今後のADとオートファジーの関連を解明するためにも学術的な意義があると考えられる。