Abstract
Introduction: Alzheimer's disease is the most common cause of dementia and one of the leading causes of morbidity and mortality among older adults. The lifetime risk of developing Alzheimer's disease is estimated to be nearly one in five for women and one in ten for men. To date, symptomatic treatments, including pharmacological therapies (cholinesterase inhibitors and memantine) and non-pharmacological interventions, have been shown to alleviate certain symptoms and improve patients' quality of life; however, these approaches do not alter the underlying progression of the disease. In recent years, disease-modifying therapies targeting the underlying pathophysiological mechanisms of Alzheimer's disease have demonstrated promising results in Phase II and Phase III clinical trials. These therapies aim to slow disease progression by reducing cerebral β-amyloid plaques, phosphorylated tau (p-tau) pathology, and other pathogenic processes. In June 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Aduhelm (aducanumab) for the treatment of Alzheimer's disease based on its ability to significantly reduce β-amyloid plaque burden. Continued approval of this indication is contingent upon verification of its clinical benefit in confirmatory post-marketing trials. From a genetic perspective, recent studies have identified 75 gene variants associated with Alzheimer's disease, including 33 previously recognized genes and 42 newly identified genetic loci linked to disease susceptibility and progression. These discoveries not only facilitate earlier diagnosis of Alzheimer's disease but also provide a scientific foundation for the development of gene-based therapeutic strategies in the near future.
