Etiology of Alzheimer's Disease

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the primary cause of dementia in the elderly. The research on AD has markedly evolved since discovering the pathological hallmarks in the brain over the past years. However, the etiology of AD has not been completely elucidated, and presently there is no cure for AD. Furthermore, despite the disease hallmarks commonly manifested in all AD cases, considerable evidence suggests complex heterogeneity of AD pathogenesis. Specifically, studies have identified several disease genes that cause or associate with AD and discovered multiple modifiable risk factors of AD, which may further aggregate the complex etiology of AD. Understanding molecular mechanisms of AD genes and modifying risk factors of AD are making it possible to develop effective interventions to prevent or cure the disease, which may in turn help understand the disease etiology. Recently, there has been keen interest in carrying out multidisciplinary investigations on AD, e.g., the studies on the molecular basis in association with neural network abnormalities in AD. Furthermore, the molecular findings on the pathogenetics of AD have provided translational proof-of-concept to intervene in AD, which has inspired clinical trials by reducing disease neuropathology related to AD genes or risk factors of AD. This article's main aim is to highlight recent progress on the mechanisms and approaches with an attempt to gain an integrated perspective of AD etiology. We envision that this article and its referenced reports may provide a valuable point of reflection that may not only acknowledge past discoveries, but also stimulate future studies, advancing the understanding of the complex etiology of AD and the development of effective therapeutics for AD.