A Presenilin 1 Mutation Associated with Familial Frontotemporal Dementia Inhibits γ-Secretase Cleavage of APP and Notch

A Presenilin 1 Mutation Associated with Familial Frontotemporal Dementia Inhibits γ-Secretase Cleavage of APP and Notch

A novel presenilin 1 mutation, insR352, associated with a frontal temporal dementia phenotype has been identified (E. A. Rogaeva et al., 2001, Neurology 57, 621–625). This mutation does not increase Aβ42 levels, but instead acts as dominant negative presenilin, decreasing amyloid β protein (Aβ) prod...

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Bibliographic Details
Main Authors: Zareen Amtul, Patrick A. Lewis, Sian Piper, Richard Crook, Matt Baker, Kirk Findlay, Andrew Singleton, Marion Hogg, Linda Younkin, Steven G. Younkin, John Hardy, Michael Hutton, Bradley F. Boeve, David Tang-Wai, Todd E. Golde
Format: Article
Language:English
Published: Elsevier 2002-03-01
Series:Neurobiology of Disease
Online Access:http://www.sciencedirect.com/science/article/pii/S0969996101904735
Description
Summary:A novel presenilin 1 mutation, insR352, associated with a frontal temporal dementia phenotype has been identified (E. A. Rogaeva et al., 2001, Neurology 57, 621–625). This mutation does not increase Aβ42 levels, but instead acts as dominant negative presenilin, decreasing amyloid β protein (Aβ) production by inhibiting γ-secretase cleavage of the Aβ precursor. The distinct clinical phenotype associated with this mutation suggests that chronic partial inhibition of γ-secretase activity may result in neurodegeneration.
ISSN:1095-953X

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