AIM/CD5L attenuates Amyloid beta at the Alzheimer's disease and prevents dementia

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16535
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49010:Pathological biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Maehara Natsumi 東京大学, 大学院医学系研究科(医学部), 助教 (90783621)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: アルツハイマー病 / アミロイドベータ / AIM / CD5L / セルフパソジェン

Outline of Final Research Achievements

Amyloid-beta plaque, responsible for Alzheimer's disease along with tau-tangle, causes cognitive decline by inducing neurological cell death and inflammation. Recently, many studies focusing on Amyloid-beta accumulation have been conducted, however, any effective therapeutic application has not been established. Here, we examined whether Apoptosis Inhibitor of Macrophage (AIM), also called CD5L, can enhance removal of the Amyloid-beta plaque, which is the "self-pathogen" in brain. In 5xFAD mice, a mouse model of Alzheimer's disease, the accumulation of Amyloid-beta was suppressed by forced expression of AIM in brain by various techniques such like Adeno-associated virus (AAV) as well the transgenic mice that overexpress AIM in their brain. To determine whether this preventive function of AIM against plaque formation can suppress the cognitive decline in 5xFAD mice, we are trying to analyze the recognition function in the presence or absence of AIM in brain.

Free Research Field

病態医科学

Academic Significance and Societal Importance of the Research Achievements

認知症は、個人および社会の負担が大きい疾患であり、アルツハイマー型認知症はその大半を占める。高齢化社会化の加速により、今後の患者数増大が見込まれるが、未だ効果的な治療法は確立されていない。本研究成果から、生体由来のタンパク質であるAIMによる、副作用の少ない新規アルツハイマー治療法の開発基盤となりうる点において、社会的意義があると考える。また、これまで腎不全や肝細胞がん、腹膜炎などにおいて、セルフパソジェンの除去作用をもち、病態を改善させることが知られてきたAIMが、脳内においても同様の作用を持つことを明らかにした点において、学術的意義があると考える。