Pathophysiology of Alzheimer's disease and mitochondrial dysfunction

2014 Fiscal Year Final Research Report

• Project/Area Number: 24591249
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: University of Tsukuba
• Principal Investigator: TAMAOKA Akira 筑波大学, 医学医療系, 教授 (50192183)
• Co-Investigator(Kenkyū-buntansha): TAKUMA Hiroshi 筑波大学, 医学医療系, 講師 (00326258) ; TOMIDOKORO Yasushi 筑波大学, 医学医療系, 講師 (80447250)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: アルツハイマー病 / アミロイドβ蛋白 / ミトコンドリア / 酸化ストレス / BACE1 / γ-secretase / アミロイド前駆体蛋白（APP）

Outline of Final Research Achievements

Mitochondrial dysfunction is implicated in the neurodegeneration in Alzheimer’s disease. Accumulation of amyloid β protein (Aβ) in mitochondria is suggested to be responsible for mitochondrial dysfunction. Then, we investigated processing of amyloid precursor protein (APP) in mitochondria in vitro studies.
Microsome and crude mitochondria fractions were obtained from human neuroblastoma SH-SY5Y cells overexpressing Swedish mutant APP by homogenization and centrifugation. By Western blot analysis. components of γ-secretase complex were similarly recovered in microsome and crude mitochondria fractions, and BACE1 was enriched in microsome fraction. After iodixanol gradient fractionation, γ-secretase complex components were recovered mainly in lysosome-enriched fractions. Taking these findings into consideration, it is unlikely that Aβ is generated from APP locally in mitochondria.

Free Research Field

神経内科学