Elucidation of the molecular pathology of Alzheimer's disease focusing on the synapses toward therapies

2014 Fiscal Year Final Research Report

• Project Area: Generation of synapse-neurocircuit pathology
• Project/Area Number: 22110003
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: The University of Tokyo
• Principal Investigator: IWATSUBO Takeshi 東京大学, 医学(系)研究科(研究院), 教授 (50223409)
• Co-Investigator(Kenkyū-buntansha): WAKABAYASHI Tomoko 東京大学, 大学院医学系研究科, 助教 (20530330) ; ITO Genta 東京大学, 大学院医学系研究科, 助教 (10431892) ; HASHIMOTO Tadafumi 東京大学, 大学院医学系研究科, 特任講師 (30334337)
• Project Period (FY): 2010-04-01 – 2015-03-31
• Keywords: アルツハイマー病 / アミロイドβペプチド / シナプス / 光遺伝学

Outline of Final Research Achievements

Massive deposition of amyloid β peptide (Aβ) as senile plaques is the pathological hallmark of Alzheimer disease (AD), although the mechanism of Aβ deposition remains unclear. In this study, we examined whether synaptic activity influences Aβ secretion and deposition in vivo. Optogenetics is a state-of-the-art technique that enables the selective control of a specific population of neurons by light. We adopted optogenetics and chronically stimulated the perforant pathway, a major input into the hippocampus, of AD model mice, and found a significant increase in Aβ deposition at the projection area of the perforant pathway. These findings implicate functional abnormalities of specific neuronal circuitry in Aβ pathology and AD.

Free Research Field

神経病理学