Identification of circulating factors triggering molecular pathological processes of Alzheimer's disease

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K21585
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Studies on the Super-Aging Society
• Research Institution: Shiga University of Medical Science
• Principal Investigator: Nishimura Masaki 滋賀医科大学, 神経難病研究センター, 教授 (40322739)
• Project Period (FY): 2019-06-28 – 2022-03-31
• Keywords: アルツハイマー病 / 老化 / 循環因子 / アミロイドβ / 脳

Outline of Final Research Achievements

Alzheimer’s diseases (AD) is the leading cause of senile dementia. Aging is the most important risk factor for AD development. Aggregation and deposition of amyloid-β peptides (Aβ) in brain triggers the pathogenetic process of AD. Aβ levels become abnormal long before onset of severe memory loss, and the strategies to prevent Aβ deposition could have great benefits for effective intervention at the preclinical stage of disease. Our study of heterochronic parabiosis using AD model mice has revealed that circulating factors of younger and older mice can suppress and promote Aβ deposition of model mice through altering the molecular expression profile in brain, respectively. We have successfully identified several molecules of which expression levels in brain were altered by the heterochronic parabiosis. These factors are candidate targets of disease-modifying therapies for AD.

Free Research Field

脳分子病態学

Academic Significance and Societal Importance of the Research Achievements

本研究により同定した因子は、アルツハイマー病に対するプレクリニカル期からの予防的医療に向けた診断と治療の両面における標的分子として有望であり、短期的には診断手法や創薬リードなどの知的財産を生むことが期待できる。長期的には、プロテイノパシーを基本病態とする脳疾患に対する先制医療の実現が本研究により加速されると予想される。プロテイノパシーは神経変性疾患に限らず、Ⅱ型糖尿病や動脈硬化など加齢に関連する主要疾患の病態でも重要視されており、それらへの効果も期待できる。