Development of apomorphine therapy targeting insulin resistance in Alzheimer's disease

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461274
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Ehime University (2015-2016); Kyushu University (2014)
• Principal Investigator: Ohyagi Yasumasa 愛媛大学, 医学系研究科, 教授 (30301336)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: アルツハイマー病 / 糖尿病 / モデルマウス / アポモルフィン / アミロイドβ蛋白 / 毒性ターン / リン酸化タウ蛋白

Outline of Final Research Achievements

Alzheimer’s disease (AD) is the major cause of dementia. A diabetes-like pathogenic mechanism in AD brain has recently been suggested, and AD is called “type-3 diabetes mellitus (DM)”. Previously, we identified apomorphine (APO) as a novel drug to promote degradation of Aβ42 accumulating in AD neurons. APO may improve the insulin resistance in AD neurons. In the present study, we established DM+AD mouse models in which injection of streptozotocin (STZ) induced type-1 DM and high-fructose diet (HFuD) induced type-2 DM in 3xTg-AD mice. Exacerbation of cognitive impairment and increases in the toxic turn Aβ42 which forms readily aggregating oligomers were more apparent in STZ-injection mice (type-1 DM) than in HFuD mice. In addition, it was indicated that toxic turn Aβ42 co-aggregates with tau oligomers in neurons. Thereafter, we will develop new therapeutic strategies of combination of APO and other DM drugs using such a DM+AD mouse models.

Free Research Field

神経内科学