Understanding the mechanisms of sundowning syndrome of Alzheimer's disease from the view of memory retrieval impairment and development of improvement methods

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K19142
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 38:Agricultural chemistry and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Kida Satoshi 東京大学, 大学院農学生命科学研究科(農学部), 教授 (80301547)
• Project Period (FY): 2022-06-30 – 2024-03-31
• Keywords: アルツハイマー型認知症 / サーカディアンリズム / 時計遺伝子 / 記憶想起 / cAMP / 夕暮れ症候群 / 必須アミノ酸 / 記憶

Outline of Final Research Achievements

Alzheimer's disease is a common worldwide problem. One of the main symptoms of Alzheimer's disease is "sundown syndrome," in which symptoms such as difficulty in speaking worsen in the evening. Still, the mechanism of this syndrome remains unknown. This study examined the hypothesis that "sundown syndrome is associated with a time-dependent impairment of memory retrieval through dysfunction of the biological clock." A mouse model of Alzheimer's disease microinfused Aβ42 into the hippocampus showed impairment of memory retrieval around 10 hours after the start of the light period, suggesting that the hypothesis was correct. Furthermore, administration of histidine, an essential amino acid, was shown to improve memory retrieval, suggesting that histidine improves memory retrieval deficits.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

本研究では、アルツハイマー型モデルマウスでは明期開始後10時間付近において時間帯依存的な記憶想起障害が観察されることを示し、認知症の症状の一つである夕暮れ症候群が時間帯依存的な想起障害と関連するとの新しい知見を得た。さらに、必須アミノ酸であるヒスチジンの投与が記憶想起を向上させることを示し、夕暮れ症候群が我々の身近な栄養素であるヒスチジンによって改善される可能性を新たに示した。