Arterial Elasticity: Linking of Cardiovascular Risks, Pulse Pressure, Dementia, Aging, and Drug Targeting

Abstract

Cerebrovascular atherosclerosis, and several other cardiovascular (or "inflamm-aging" type) diseases, are more frequent and advanced in subjects with Alzheimer's disease compared with normal aging. In addition, the observed pathogenic link to dementia (and its associated cerebral microvascular damage) is readily explained by alterations of arterial elasticity. A therapeutic strategy to delay dementia could be based upon localized drug delivery, using lipid nanocarriers (i.e., biobased nanoemulsion technology), targeted toward a major serum amyloid A (SAA) receptor involved in certain proinflammatory, SAA-mediated, cell signaling events. Moreover, by incorporating drug molecules into such lipid nanocarriers, one can obtain a "combination therapeutic" capable of targeting simultaneously (via cell-surface scavenger receptors) a variety of cell types, each potentially implicated in Alzheimer's disease and/or dementia, for focused drug delivery in vivo.