Development of a novel in vitro model of Alzheimer´s disease and its application to high-throughput screening assays

Abstract

Alzheimer’s disease is the leading neurodegenerative disorder worldwide and the most prevalent cause of dementia, accounting for 60 to80% of all cases. With an estimated 50 million individuals affected globally and the incidence projected to triple by 2050, AD represents a growing public health and socioeconomic burden. A small percentage of AD cases ,1 to 5%, are familial in origin, caused by mutations in genes such as APP, PSEN1/2, and MAPT, which influence the amyloidogenic pathway or tau protein processing. Conversely, the sporadic form of AD, which constitutes the majority of cases, is linked to complex genetic and environmental interactions, including aging, previous pathologies, oxidative stress, and chronic inflammation. Alzheimer’s pathology is characterized by a progressive cognitive decline driven by the loss of synaptic integrity, neuronal death, and chronic neuroinflammation. These neurodegenerative changes and progression of the disease are underpinned by key hallmark features such as amyloid-beta and tau deposits.