Analysis of metabolic pathways of apoE-containing lipoproteins in the brain for elucidation of sporadic Alzheimer's disease

• Project/Area Number: 18K10995
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 59040:Nutrition science and health science-related
• Research Institution: Ehime University
• Principal Investigator: Fujino Takahiro 愛媛大学, 学術支援センター, 准教授 (40292312)
• Project Period (FY): 2018-04-01 – 2024-03-31
• Project Status: Completed (Fiscal Year 2023)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
• Keywords: アポE / リポタンパク / HDL / リポタンパク受容体 / アルツハイマー / アポＥ / アポリポタンパクE / 中枢神経系 / コレステロール

Outline of Final Research Achievements

Expression and purification systems were established for glycosylated human ApoE2, 3, and 4, as well as ApoE mutants without glycosylation. ApoE-nHDL was prepared using these systems. No uptake of ApoE-nHDL into neurons was observed when it was injected into the ventricles of a mouse model of nerve injury. Additionally, no change in aggregates or phosphorylation state of the mutant tau protein was observed when the ApoEs and familial mutant tau protein were introduced into cultured neuronal cells with fibrotic tau protein seeds.

Academic Significance and Societal Importance of the Research Achievements

本研究では、これまでほとんど注目されてこなかったアポEの糖鎖修飾が与えるアポEアイソフォーム間の生理機能の違い、特に神経細胞への影響を解析した。本研究による中枢神経系におけるアポE含有リポタンパク代謝の解析を通じて、散発性アルツハイマー病発症におけるアポＥ4の役割を解明することで、病態解明や予防、さらには治療の基礎を築くためのいくつかの知見が得られたと考えている。