Vascular models of Alzheimer's disease: An overview of recent in vitro models of the blood-brain barrier

Alzheimer's disease (AD) remains an overwhelming epidemiologic and economic burden on our healthcare systems, affecting an estimate of 11 % of individuals aged 65 years and older. Increasing evidence of the role of the blood-brain barrier (BBB) in AD pathology lends support to the vascular hypothesis of AD, which posits that damage to cerebral vasculature and impairments to cerebral blood flow are major contributors to neurodegeneration in AD. While the question remains whether the dysfunction of the BBB is the cause or consequence of the disease, understanding of the relationship between vascular pathology and AD is growing increasingly complex, warranting the need for better tools to study vasculature in AD. This review provides an overview of AD models in the context of studying vascular impairments and their relevance in pathology. Specifically, we summarize opportunities in in vitro models, cell sources, and phenotypic observations in sporadic and familial forms of AD. Further, we describe recent advances in generating models which recapitulate in vivo characteristics of the BBB in AD through the use of microfluidics, induced pluripotent stem cells (iPSC), and organoid technologies. Finally, we provide a searchable database of reported cell-based models of pathogenic AD gene variants.