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

In recent years, important progress has been made in uncovering genes implicated in Alzheimer's disease (AD). Three causal genes have been identified in which mutations cause familial presenile AD: the amyloid precursor protein gene and the presenilin 1 and 2 genes. Additionally, the epsilon 4 allele of the apolipoprotein E gene was shown to be a major risk factor for AD. Despite the genetic heterogeneity, all of these genes work through a common mechanism, i. e. increasing the amount and deposition of the amyloid beta peptide (A beta) in brain triggering AD-related neuronal degeneration. Therefore, the levels of A beta and of the factors involved in its production and deposition are important in the neuropathogenesis of AD. Regulation of transcription of AD genes might therefore be an important player in the neurodegenerative process. In this review, we describe the major features of transcriptional regulation of the known AD genes and the implications of variable expression levels on susceptibility to AD.