Vascular Risks, Aging, and Late-Onset Dementia: Overlapping Etiologies Point to 'Scavenger Receptor'-Mediated Therapeutics

Abstract

Early changes in systemic vascular stiffness and endothelial function can contribute to altered cerebrovascular hemodynamics and impaired cognitive function; additionally, these vascular changes point to potential targets for prevention and treatment strategies in people with mild cognitive impairment. Although the pathogenic mechanisms underlying these vascular changes are heterogeneous and complex, one common feature is the development of cerebral blood flow (CBF) dysregulation, resulting in chronic cerebral hypoperfusion (CCH) and subsequently an insufficient blood supply to the brain. However, the incorporation of drugs, or other bioactive molecules, into specifically a "high density lipoprotein-like" ("HDL-like") lipid nanocarrier can result in the production of a multitasking "combination therapeutic" – capable of targeting cell-surface scavenger receptors (mainly SR-BI). Such targeting behavior of this proposed (biomimetic-nanocarrier) therapeutic vehicle can facilitate the nanocarrier's enhanced endocytosis into various target cells which, in turn, increases the likelihood that this multitasking "combination therapeutic" provides some enhanced efficacy at different stages of dementia.