Alzheimer's Disease: The Link Between Amyloid-β and Neurovascular Dysfunction

While prevailing evidence supports that the amyloid cascade hypothesis is a key component of Alzheimer's disease (AD) pathology, many recent studies indicate that the vascular system is also a major contributor to disease progression. Vascular dysfunction and reduced cerebral blood flow (CBF) occur prior to the accumulation and aggregation of amyloid-beta (A beta) plaques and hyperphosphorylated tau tangles. Although research has predominantly focused on the cellular processes involved with A beta-mediated neurodegeneration, effects of A beta on CBF and neurovascular coupling are becoming more evident. This review will describe AD vascular disturbances as they relate to A beta, including chronic cerebral hypoperfusion, hypertension, altered neurovascular coupling, and deterioration of the blood-brain barrier. In addition, we will describe recent findings about the relationship between these vascular defects and A beta accumulation with emphasis on in vivo studies utilizing rodent AD models.