Where does the degeneration in Alzheimer's disease begin, and how are memory impairments caused?

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K19447
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Kyoto University
• Principal Investigator: Nobukatsu Sawamoto 京都大学, 医学研究科, 教授 (90397547)
• Co-Investigator(Kenkyū-buntansha): 綾木 孝 京都大学, 医学研究科, 助教 (60749555)
• Project Period (FY): 2021-07-09 – 2024-03-31
• Keywords: 7テスラMRI / 嗅内野 / 側頭葉皮質 / マイネルト基底核 / アミロイドβ / タウ

Outline of Final Research Achievements

Based on the analysis of autopsied brains in Alzheimer's disease, the prevailing view is that "neurodegeneration begins in the entorhinal cortex of the temporal lobe and progresses to the nucleus basalis of Meynert, leading to the development of memory impairments." Alternatively, there has also been a proposal that "degeneration begins in the nucleus basalis of Meynert and that this alone does not lead to the development of memory impairments." In this study, we conducted ultra-sensitive and high-resolution magnetic resonance imaging along with symptom evaluation. The present results showed a strong correlation between degeneration in the nucleus basalis of Meynert and the temporal lobe cortex. In addition, mediation analysis demonstrated that degeneration in the nucleus basalis of Meynert was involved in the onset of verbal memory impairments through the mediation of degeneration in the temporal lobe cortex.

Free Research Field

病態神経科学

Academic Significance and Societal Importance of the Research Achievements

神経変性疾患は、異常タンパク質が細胞間を伝播することによって神経細胞死が一定の様式で進展するという仮説が受け入れられつつあり、現在、異常タンパク質を取り除く治療法の開発努力が継続されている。この異常タンパク質の除去については、神経細胞が変性した段階で行っても治療による改善は難しいという見方が、アルツハイマー病を対象としたこれまでの治験の結果から有力視されている。したがって、異常タンパク質を除去する根本的治療が開発できれば「変性がどこから始まってどのように広がるのか、変性の広がりと臨床症候はどう対応するのか」は治療介入時期の決定に必須の情報となる。