Alzheimer’s disease is characterized by amyloid plaques formed via cleavage of amyloid precursor protein (APP). Jonsson et al. studied coding variants in APP gene in a set of whole-genome sequence data from 1,795 Icelanders, searching for low-frequency variants in APP gene with a significant effect on the risk of Alzheimer’s disease.
A coding mutation (A673T) was identified in the APP gene that protects against Alzheimer’s disease and cognitive decline. The mutation causes a 40% reduction in the formation of amyloidogenic peptides in vitro. This substitution is adjacent to the aspartyl protease Î²-site in APP. The authors conclude that this finding provides proof of principle for the hypothesis that reducing the Î²-cleavage of APP may protect against Alzheimer’s disease. Â
A mutation in APP protects against Alzheimer’s disease and age-related cognitive decline. Jonsson et al. Nature. 2012 Jul 11. doi: 10.1038/nature11283. [Epub ahead of print] PMID: 22801501
posted by Yannis Trakadis, MD