Alzheimer's disease: Exploration of combination therapy with food-derived amyloid-beta peptide modulators and environmental therapy.

2017 Fiscal Year Final Research Report

• Project/Area Number: 26430058
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Nerve anatomy/Neuropathology
• Research Institution: Saitama Medical University
• Principal Investigator: MORI TAKASHI 埼玉医科大学, 医学部, 教授 (60239605)
• Research Collaborator: KOYAMA NAOKI 埼玉医科大学 ; OKADA SACHIKO 埼玉医科大学 ; RYUMAE SHINYA 埼玉医科大学 ; MAEDA MASAHIRO 免疫生物研究所 ; MARUYAMA NOBUHIRO 免疫生物研究所 ; TAN JUN University of South Florida ; TOWN TERRENCE Keck School of Medicine of the University of Southern California
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: アルツハイマー病 / 遺伝子改変マウス / フェノール化合物 / 抗炎症効果 / 抗酸化効果 / シナプス関連蛋白 / 認知機能 / 行動機能

Outline of Final Research Achievements

To examine whether combination therapy further modifies versus single treatment, we treated with an alpha-secretase promotor and a beta-secretase modulator to the model mouse of Alzheimer's disease (AD) (PSAPP mouse). Combination therapy further remediated most behavioral outcome measures versus either single treatment. Moreover, double-treated PSAPP mice had further amelioration of cerebral amyloidosis compared to single treatment alone. Combination therapy elevated nonamyloidogenic soluble APP-alpha and ADAM10, and downregulated expression of amyloidogenic β-carboxyl-terminal APP fragment and BACE1. In concert, the ratio of beta- to alpha-carboxyl-terminal APP fragment was decreased. In toto, combined treatment shifted APP cleavage toward the non-amyloidogenic pathway. Further co-treatment effects included amelioration of neuroinflammation, oxidative stress, and synaptotoxicity. Therefore, we offer preclinical evidence that combination therapy is a promising AD therapeutic approach.

Free Research Field

神経病理学