Pathogenesis of Alzheimer's disease caused by type 1 diabetes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K06466
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 42040:Laboratory animal science-related
• Research Institution: University of Fukui
• Principal Investigator: Tokunaga Akinori 福井大学, ライフサイエンス支援センター, 准教授 (70549451)
• Co-Investigator(Kenkyū-buntansha): 多田 敬典 至学館大学, 健康科学部, 教授 (20464993)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アルツハイマー病 / 糖尿病 / インスリンシグナル

Outline of Final Research Achievements

There is an increasing awareness that diabetes has an effect on the CNS and that diabetes is a risk factor for AD. We performed the analysis of post translational protein modifications in the hippocampus and frontal cortex of AD and type 1diabetes model mice, and also examined their correlation with cognitive function.
Phosphorylation of AKT, GSK3β were similarly affected in AD and insulin-deficient STZ mice, despite significantly different blood glucose and plasma insulin levels. Then, we observed common signaling changes prior to the onset of cognitive decline. Furthermore, abnormally phosphorylated tau was observed in the brains of STZ mouse. Although type 1diabetes and AD have different primary etiologies, both diseases share some abnormalities in the brain. Our data point to deficits in common signaling pathway in both neurodegenerative diseases and support the idea that hyperglycemia may cause brain disorders, associated to AD.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

高齢化の進展に伴い認知症患者の更なる増加が見込まれており、その対策は喫緊の課題となっている。アルツハイマー病と糖尿病には、脳での病態進行において共通する分子基盤があることが明らかにされつつある。これまでにAD患者の死後脳解析からも糖代謝に関わるインスリンシグナルの質的変化が観察されている。今回1型糖尿病モデルにおいても同様のシグナル変化が確認され、血中インスリン量に依存しないシグナル誘導経路の存在が示唆された。今後の研究発展によりAD発症に関わる分子基盤の解明や新たな治療法の開発が期待される。