Genes associated with Alzheimer's disease: an overview and current status.

Alzheimer's disease (AD) is a progressive, neurodegenerative disease and the most common form of dementia in elderly people. It is an emerging public health problem that poses a huge societal burden. Linkage analysis was the first milestone in unraveling the mutations in APP, PSEN1, and PSEN2 that cause early-onset AD, followed by the discovery of apolipoprotein E-ε4 allele as the only one genetic risk factor for late-onset AD. Genome-wide association studies have revolutionized genetic research and have identified over 20 genetic loci associated with late-onset AD. Recently, next-generation sequencing technologies have enabled the identification of rare disease variants, including unmasking small mutations with intermediate risk of AD in PLD3, TREM2, UNC5C, AKAP9, and ADAM10. This review provides an overview of the genetic basis of AD and the relationship between these risk genes and the neuropathologic features of AD. An understanding of genetic mechanisms underlying AD pathogenesis and the potentially implicated pathways will lead to the development of novel treatment for this devastating disease.