Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by loss of memory and cognitive function. A key neuropathological event in AD is the accumulation of amyloid-β (Aβ) peptide. The production and clearance of Aβ in the brain are regulated by a large group of genes. The expression levels of these genes must be fine-tuned in the brain to keep Aβ at a balanced amount under physiological condition. Misregulation of AD genes has been found to either increase AD risk or accelerate the disease progression. In recent years, important progress has been made in uncovering the regulatory elements and transcriptional factors that guide the expression of these genes. In this review, we describe the mechanisms of transcriptional regulation for the known AD genes and the misregualtion that leads to AD susceptibility.