Cerebrovascular contributions to Alzheimer's disease pathophysiology and potential therapeutic interventions in mouse models

The inter-relationship between vascular dysfunction and Alzheimer's disease pathology is not clearly understood; however, it is clear that the accumulation of amyloid-beta peptide and loss of vascular function contribute to the cognitive decline detected in patients. At present, imaging modalities can monitor the downstream effects of vascular dysfunction such as cerebral blood flow alterations, white and gray matter lacunes, and ischemic lesions; however, they cannot distinguish parenchymal plaques from cerebrovascular amyloid. Much of our understanding regarding the relationship between amyloid and vascular dysfunction has come from longitudinal population studies and mouse models. In this review, we will discuss the breadth of data generated on vascular function in mouse models of Alzheimer's disease and cerebrovascular amyloid angiopathy. We will also discuss therapeutic strategies targeting the reduction of cerebrovascular amyloid angiopathy and improvement of vascular function.