Treating early dementia: Drug targeting and circumventing the blood-brain barrier

Over past decades, a frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, diabetes, obesity, hypertension, smoking, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. These findings indicate that preservation of healthy cerebrovascular endothelium can be an important therapeutic target. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted "lipid-coated microbubble/nanoparticle-derived" (LCM/ND) lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), making it possible for various Alzheimer's-related cell types to be simultaneously searched out for localized drug treatment in vivo. Besides targeting cell-surface SR-BI, the proposed LCM/ND-nanoemulsion combination therapeutic(s) include a characteristic lipid-coated microbubble (LCM) subpopulation (i.e., a stable LCM suspension); such LCM would facilitate accomplishing transcranial sonoporation (if additionally, desired for the Alzheimer's patient) and assist in advancing sonoporation to the clinic.