The early contribution of cerebrovascular factors to the pathogenesis of Alzheimer's disease

Alzheimer's disease (AD) and cerebrovascular disorders are the leading causes of dementia in our ageing population. Given that the progression of neuropathological changes in the brains of AD patients initiates several years, and even decades, before the diagnosis of dementia, a great effort has been made to identify potentially modifiable factors that contribute to the pathogenesis of sporadic late-onset AD. Among these factors, cerebrovascular disease and microvascular alterations seem to bilaterally interact with the underlying AD pathology, affecting the progression of cognitive deficits. In addition, cerebrovascular dysfunction has emerged as an early event in AD, encompassing changes in virtually all cell types of the neurovascular unit, including bone marrow-derived cells, astrocytes, pericytes, vascular smooth muscle cells and endothelial cells. In this review, we discuss recent studies implicating cerebrovascular factors in the pathogenesis of AD. We also discuss how the impairment of mechanisms of brain regeneration, such as neurogenesis and angiogenesis, might be related to the vascular dysfunction. Finally, we briefly discuss several therapeutic options targeting the vascular system, which might represent an interesting strategy for preventing or delaying the onset of dementia in AD.