2011 Fiscal Year Final Research Report

The impact of clinical presenilin mutations on amyloid formation in the brains of familial Alzheimer disease

Research Project

Project/Area Number	22890251
Research Category	Grant-in-Aid for Research Activity Start-up
Allocation Type	Single-year Grants
Research Field	Neurology
Research Institution	National Center for Geriatrics and Gerontology
Principal Investigator	OIKAWA Naoto 独立行政法人国立長寿医療研究センター, 認知症先進医療開発センター治療薬探索研究部, 流動研究員 (00583585)
Project Period (FY)	2010 – 2011
Keywords	神経変性疾患 / 認知症 / アルツハイマー病 / プレセニリン / γセクレターゼ / アミロイドβプロテイ / アミロイド / ガングリオシド
Research Abstract	To clarify the significance of clinical presenilin mutations in amyloid formation in the brains of familial Alzheimer disease, we examined whetherγ-secretase inhibition, which seems to be induced by the presenilin mutations, alters the levels of membrane lipids, including GM1-ganglioside, which is an inducer of amyloid formation, in vitro. Under pharmacological inhibition ofγ-secretase activity, levels of gangliosides, including GM1-ganglioside, increased at neuritic terminals, which are the initial sites of amyloid formation, of differentiated PC12 cells. This result suggests that clinical presenilin mutations can induce amyloid formation via the alteration of membrane lipid environment in brains.

(2 results)