Characterization of gamma-secretase activity in the brain and its significance in the development of Alzheimer's disease

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500433
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurochemistry/Neuropharmacology
• Research Institution: Hokkaido University
• Principal Investigator: MORISHIMA Maho 北海道大学, 薬学研究科(研究院), 客員准教授 (50204722)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: アミロイドβタンパク質 / アルツハイマー病 / γセクレターゼ

Outline of Final Research Achievements

To learn whether altered brain γ-secretase activity contributes to the deposition of amyloid β-protein (Aβ) in the sporadic Alzheimer’s disease patients, γ-secretase activity in the brain was assessed using in vitro reconstituted Aβ generation system in the presence of CHAPSO. γ-Secretase activity in the brain was regulated in the developmental stage-dependent manner．The regional distribution and age-dependent alteration of the γ-secretase activity were little correlated with various indexes of Aβ deposition as well as risk factors for AD. Thus, the quantitative alteration of γ-secretase activity during aging may not be involved in the pathological Aβ deposition in the brain. Further analysis regarding the modulation of γ-secretase activity (variability of cleavage sites) in the brain is ongoing.

Free Research Field

神経化学