A novel missense mutation in the presenilin-1 gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy

doi:10.1016/S0304-3940(97)00569-7

Neuroscience Letters

Volume 232, Issue 1, 22 August 1997, Pages 29-32

https://doi.org/10.1016/S0304-3940(97)00569-7 Get rights and content

Abstract

A number of missense mutations associated with early-onset familial Alzheimer's disease have been reported in the presenilin-1 gene. The mutations were demonstrated to cluster in specific regions of the protein. We report here a novel missense mutation at the C-terminus of the third transmembrane domain in the presenilin-1 protein in a family of Japanese origin with early-onset Alzheimer's disease. This mutation is located at a site that is different from the sites at which mutations are known to cluster. Although the clinical phenotype is similar to those of pedigrees associated with other presenilin-1 mutations, postmortem examination of this pedigree revealed heavy amyloid deposits in the walls of small meningeal arteries as well as around small vessels within the brain parenchyma. These results indicate that a mutation at the C-terminus of the third transmembrane domain in the presenilin-1, which is a novel site for mutations, may play a key role in Alzheimer's pathogenesis.

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Acknowledgements

We thank the physicians and staff of Hyogo Institute for Aging Brain and Cognitive Disorders, Japan for performing the clinical evaluation. A part of this study was supported by grants from the Japan Pharmacopsychiatry Research Foundation, and the Hyogo Creation and Technology Association.

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A novel missense mutation in the presenilin-1 gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy

Abstract

Section snippets

Acknowledgements

Neuron

Trends Neurosci.

FEBS Lett.

Neuron

Early-onset Alzheimer's disease caused by mutations at codon 717 of the beta-amyloid precursor protein gene

Nature

Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease

Nature

Complete analysis of the presenilin 1 gene in early onset Alzheimer's disease

NeuroReport

The clinical phenotype of two missense mutations in the presenilin 1 gene in Japanese patients

Ann. Neurol.

Two novel (M233T and R278T) presenilin-1 mutations in early-onset Alzheimer's disease pedigrees and preliminary evidence for association of presenilin-1 mutations with a novel phenotype

NeuroReport