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PMID: 8599933 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Expression of V642 APP mutant causes cellular apoptosis as Alzheimer trait-linked phenotype.

The EMBO journal ·Vol. 15 ·No. 3 ·1996-02-01 ·Pages 498-509

Yamatsuji T, Okamoto T, Takeda S, Murayama Y, Tanaka N, Nishimoto I

Abstract

APP is a transmembrane precursor of beta-amyloid. In dominantly inherited familial Alzheimer's disease (FAD), point mutations V6421, V642F and V642G have been discovered in APP695. Here we show that expression of these mutants (FAD-APPs) causes a clone of COS cells to undergo apoptosis associated with DNA fragmentation. Apoptosis by the three FAD-APPs was the highest among all possible V642 mutants; normal APP695 had no effect on apoptosis, suggesting that apoptosis by APP mutants in this system is phenotypically linked to the FAD trait. FAD-APP-induced apoptosis was sensitive to bcl-2 and most probably mediated by heteromeric G proteins. This study presents a model system allowing analysis of the mechanism for FAD-APP-induced cytotoxicity.

MeSH Terms
Alzheimer Disease/genetics,metabolism,pathology Amino Acid Sequence Amyloid beta-Protein Precursor/genetics,physiology Animals Apoptosis/genetics Base Sequence Clone Cells DNA/metabolism DNA Primers/genetics DNA, Complementary/genetics Humans Models, Biological Molecular Sequence Data Mutagenesis, Site-Directed Phenotype Point Mutation
Chemicals
Amyloid beta-Protein Precursor DNA Primers DNA, Complementary DNA
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Yamatsuji T
Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Okamoto T
Takeda S
Murayama Y
Tanaka N
Nishimoto I
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-02-01
Pages
498-509
Language
English
Region
England
NLM ID
8208664
PMCID
PMC449968
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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