Exploration of the pathological relationship between diabetes and Alzheimer's disease through disruption of soluble apoE receptor shearing and release

2023 Fiscal Year Final Research Report

• Project/Area Number: 18K19526
• 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: Toho University
• Principal Investigator: Bujo Hideaki 東邦大学, 医学部, 教授 (80291300)
• Project Period (FY): 2018-06-29 – 2024-03-31
• Keywords: アルツハイマー病 / アポEレセプター / 免疫学的解析 / プロセシング異常 / プロテアーゼ / 脳組織

Outline of Final Research Achievements

The aim of this study was to investigate that the possible involvement of disturbed proteinase action for the processing of apo E receptor LR11, which has been proposed in the pathological basis of diabetes mellitus, in that of Alzheimer’s disease. The immunohistochemical analysis of brain tissues from patients with Alzheimer’s disease showed that the LR11 staining levels in the neurons, which were decreased with patients with apo E genotype E4, increased in the early clinical stage. The LR11 staining levels were different between the results using antibodies detecting for the ectodomain region and the C-terminal region, respectively. The abnormal processing of LR11 by the disturbed action of proteinases, which play a key role in the trans-differentiation of adipocytes, may be involved in the pathological basis of Alzheimer’s disease.

Free Research Field

病態検査学

Academic Significance and Societal Importance of the Research Achievements

LR11 は研究代表者らが動脈硬化巣に発現するアポEレセプターとしてクローニングした新規遺伝子で、プロテアーゼによりプロセシングを受けて可溶性レセプターとなり、その血中濃度は血管病に加えて糖尿病やアルツハイマー病の病態を反映する。本研究の学術的意義は、プロテアーゼ作用障害によるレセプタープロセシング異常が、脂肪細胞トランスディファレンシエーション過程の障害のみならず、アルツハイマー病の病態基盤に関わる可能性を示したことである。本研究成果は、糖尿病患者がアルツハイマー病を合併しやすいという社会的課題への新規の治療開発のアプローチを提示したことに意義がある。