Genetic variations in promoter sequences that alter gene expression play a prominent role in increasing susceptibility to complex diseases. Also, expression levels of APP are essentially regulated by its core promoter and 5’ upstream regulatory region and correlate with amyloid beta levels in Alzheimer disease (AD) brains.
In an article published in the July 2006 issue of American Journal of Human Genetics (Vol. 78, pp. 936-946), Theuns et al. systematically sequenced the proximal promoter (-766/+204) and two functional distal regions (-2634/-2159 and -2096/-1563) of APP in two independent AD series with onset ages less than or equal to 70 years (Belgian sample, n = 180; Dutch sample, n = 111) and identified eight novel sequence variants.
The present study provides evidence that APP-promoter mutations that significantly increase APP expression levels are associated with AD.
Christine Van Broeckhoven, Neurodegenerative Brain Diseases Group, Department of Molecular Genetics, Flanders Interuniversity Institute of Biotechnology, Laboratories of Neurogenetics, Institute Born-Bunge, University of Antwerp, Rotterdam.
Abstract available online.
(C) American Journal of Human Genetics.
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