Contributions of vascular ageing to late-onset Alzheimer's disease.

Late-onset Alzheimer's disease (LOAD) is an age-related disease that is strongly associated with vascular risk factors and cerebrovascular impairments. As such, changes in the vasculature with advancing age likely contribute to LOAD, but the mechanisms underlying these contributions remain incompletely understood. With advancing age, there is dysregulation of cerebral blood flow, impairment of neurovascular coupling, and increased blood-brain barrier permeability, which may initiate or contribute to the neuropathology associated with LOAD. Changes to the vasculature outside of the brain, including increases in blood pressure and arterial stiffness, may initiate age-related cerebrovascular impairments. Age-related increases in oxidative stress and inflammatory signalling, as well as contributions to LOAD-related neuropathology, such as amyloid-β and hyperphosphorylated tau, impair cerebrovascular cells. In this review, we summarize the evidence for the role of vascular ageing in LOAD, describing age-related cerebrovascular impairments and their causes.