The genes associated with early-onset Alzheimer’s disease

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that accounts for the most cases of dementia, which is characterized by the deposition of dense plaques of amyloid beta (Aβ) plaques and neurofibrillary tangles consisting of hyperphosphorylated tau. The two main types of AD can be classified as early-onset AD (EOAD, onset < 65 years) and late-onset AD (LOAD, onset ≥ 65 years). Evidence from family and twin studies indicate that genetic factors are estimated to play a role in at least 80% of AD cases. The first milestone with linkage analysis revealed the mutations in APP, PSEN1, and PSEN2 genes that cause EOAD. But pathogenic mutations in these three genes can only explain a small fraction of EOAD families. The additional disease-causing genes have not yet been identified. This review provides an overview of the genetic basis of EOAD and the relationship between the functions of these risk genes and the neuropathologic features of AD. A better understanding of genetic mechanisms underlying EOAD pathogenesis and the potentially molecular mechanisms of neurodegeneration will lead to the development of effective diagnosis and treatment strategies for this devastating disease.