Microvascular Alterations in Alzheimer's Disease

Alzheimer's disease (AD) is a neurodegenerative disorder associated with continual decline in cognition and ability to perform routine functions such as remembering familiar places or understanding speech. For decades, amyloid beta (A beta) was viewed as the driver of AD, triggering neurodegenerative processes such as inflammation and formation of neurofibrillary tangles (NFTs). This approach has not yielded therapeutics that cure the disease or significant improvements in long-term cognition through removal of plaques and A beta oligomers. Some researchers propose alternate mechanisms that drive AD or act in conjunction with amyloid to promote neurodegeneration. This review summarizes the status of AD research and examines research directions including and beyond A beta, such as tau, inflammation, and protein clearance mechanisms. The effect of aging on microvasculature is highlighted, including its contribution to reduced blood flow that impairs cognition. Microvascular alterations observed in AD are outlined, emphasizing imaging studies of capillary malfunction. The review concludes with a discussion of two therapies to protect tissue without directly targeting A beta for removal: (1) administration of growth factors to promote vascular recovery in AD; (2) inhibiting activity of a calcium-permeable ion channels to reduce microglial activation and restore cerebral vascular function.

Automated summary

Alzheimer's disease is a neurodegenerative disorder characterized by cognitive decline, with Aβ traditionally viewed as the primary driver but lacking effective therapeutics. Alternate mechanisms and the impact of aging on microvasculature are also considered significant factors in AD research.