Intercellular Propagation Among Different Tau Species Using a Tauopathy Cell Model

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K15725
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 52020:Neurology-related
• Research Institution: Niigata University
• Principal Investigator: Ishiguro Takanobu 新潟大学, 医歯学総合病院, 助教 (40929634)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: タウオパチー / 神経細胞興奮 / β-アミロイド / タウ

Outline of Final Research Achievements

We focused on the differences in pathogenesis between Alzheimer's disease (AD) and non-AD tauopathy, examining the interrelationships between the production, extracellular secretion, and neuronal excitotoxicity of pathological proteins associated with AD (Aβ, tau), and proceeded to verify using neuronal culture cells. We demonstrated: ① that APP processing varies depending on glutamate concentration for Aβ production, ② that extracellular tau secretion depends on Aβ levels and is inhibited by suppressing Aβ production, and ③ that introduction of mutant tau suppresses the amyloid production pathway. The possibility that APP processing differs between AD and non-AD tauopathy was suggested.

Free Research Field

脳神経内科学

Academic Significance and Societal Importance of the Research Achievements

ADに関連した病的蛋白（Aβ，タウ）の産生や細胞外放出の機序を細胞実験レベルで検証した。本研究においては、Aβ産生にかかわる、APP processingがADと非ADタウオパチーで異なることが示唆された。今後、この機序を明らかにすることが、タウオパチーの病態解明について新たな着想点となる可能性がある。