Published in
American Association for the Advancement of Science, Science, 5920(323), p. 1473-1477, 2009
Links
- ORCID
- ORCID
- American Association for the Advancement of Science
- [www.ncbi.nlm.nih.gov] | PDF
- [europepmc.org] | PDF
- [www.researchgate.net] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [www.ncbi.nlm.nih.gov] | PDF
- [air.unimi.it] | PDF
Tools
A Recessive Mutation in the APP Gene with Dominant-Negative Effect on Amyloidogenesis
,
Marcella Catania ,
Michela Morbin,
Giacomina Rossi,
Silvia Suardi,
Giulia Mazzoleni,
Marco Merlin,
Anna Rita Giovagnoli,
Sara Prioni,
Alessandra Erbetta,
Chiara Falcone,
Marco Gobbi,
Laura Colombo,
Antonio Bastone,
Marten Beeg
and other authors.
Full text: Download
Abstract
beta-Amyloid precursor protein (APP) mutations cause familial Alzheimer's disease with nearly complete penetrance. We found an APP mutation [alanine-673-->valine-673 (A673V)] that causes disease only in the homozygous state, whereas heterozygous carriers were unaffected, consistent with a recessive Mendelian trait of inheritance. The A673V mutation affected APP processing, resulting in enhanced beta-amyloid (Abeta) production and formation of amyloid fibrils in vitro. Co-incubation of mutated and wild-type peptides conferred instability on Abeta aggregates and inhibited amyloidogenesis and neurotoxicity. The highly amyloidogenic effect of the A673V mutation in the homozygous state and its anti-amyloidogenic effect in the heterozygous state account for the autosomal recessive pattern of inheritance and have implications for genetic screening and the potential treatment of Alzheimer's disease.