Transcriptional regulation of Alzheimer's disease genes: implications for susceptibility

In recent years, important progress has been made in uncovering genes impli cated in Alzheimer's disease (AD), Three causal genes have been identified in which mutations cause familial presenile AD: the amyloid precursor prote in gene and the presenilin 1 and 2 genes. Additionally, the epsilon4 allele of the apolipoprotein E gene was shown to be a major risk factor for AD. D espite the genetic heterogeneity, all of these genes work through a common mechanism, i.e. increasing the amount and deposition of the amyloid beta pe ptide (A beta) in brain triggering AD-related neuronal degeneration. Theref ore, the levels of A beta and of the factors involved in its production and deposition are important in the neuropathogenesis of AD. Regulation of tra nscription of AD genes might therefore be an important player in the neurod egenerative process. In this review, we describe the major features of tran scriptional regulation of the known AD genes and the implications of variab le expression levels on susceptibility to AD.