The imbalance of vascular molecules in Alzheimer's disease.

The vascular system plays an integral role during Alzheimer's disease (AD). Both systemic circulatory changes and alterations directly within the brain vasculature have been suggested to contribute to both the onset and progression of neurological conditions such as AD. It is now well established that vascular risk factors including hypertension, diabetes, obesity, atherosclerosis, metabolic syndrome, and stroke significantly increase one's risk of later developing AD. Research within the last decade has begun to identify specific vascular molecules associated with such risk factors as well as elucidate the biological role they may play in the pathological processes linked to AD. This review aims to provide an overview of some of the key molecules within vascular cells and circulating in blood that have been identified to be altered in AD pathogenesis. In particular, the vascular-specific transcription factors MEOX2, MYOCD, and SRF, genetic risk factor APOE4, transport proteins LRP1 and RAGE, and circulating molecules such as sLRP1, homocysteine, and albumin are discussed. I aim to clarify how these identified vascular molecules may help to predict, explain, and influence the incidence AD. A strong emphasis is placed on the concept that these molecules play overlapping roles in cardiovascular disease progression, neurovascular dysfunction, and amyloid-β pathology. The studies reviewed here have identified vascular-based molecular targets in AD and thus provide new therapeutic avenues for the treatment of this devastating disease.