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To arrive at a clear and atomically realistic representation of the process of ionic screening, a model with the following necessary and justifiable constraints was devised. 1) The minimum internuclear distance (IND) between a negative site on the membrane and a cation screening the site is equal to the sum of the site's "equivalent" radius (rs) + the diameter of a water molecule (approximately 2.8 A) + crystal radius of the cation (rc). 2) The average value for the dielectric constant (D) over IND is given by D approximately 80 ((IND - rs - rc)/IND). When this simple atomic model for ionic screening is employed in conjunction with equilibrium ion-selectivity theory, it is possible to predict quantitatively, from coulombic energy calculations, the secondary stereospecific actions of certain alkaline-earth cations as well as the predominant screening effect of these divalent cations at the surfaces of different types of membranes. The model also successfully predicts the transition from a predominantly screening situation to a predominantly binding situation, which was observed experimentally when negative surface charge density was decreased in nerve.

Owing to the complexity of neurodegenerative diseases, multiple cellular types need to be targeted simultaneously in order for a given therapy to demonstrate any major effectiveness. Ultrasound-sensitive coated microbubbles (in a targeted nanoemulsion) are available. Versatile small-molecule drug(s) targeting multiple pathways of Alzheimer's disease pathogenesis are known. By incorporating such drug(s) into the targeted LCM/ND lipid nanoemulsion type, one obtains a multitasking combination therapeutic for translational medicine. This multitasking therapeutic targets cell-surface scavenger receptors (mainly SR-BI), making 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 substantially reduce the acoustic power levels needed for accomplishing temporary noninvasive (transcranial) ultrasound treatment, or sonoporation, if additionally desired for the Alzheimer's patient.

By incorporating appropriate drug(s) into lipid (biobased) nanocarriers, one obtains a combination therapeutic for dementia treatment that targets certain cell-surface scavenger receptors (mainly class B type I, or “SR-BI”) and thereby crosses the blood-brain barrier. The cardiovascular risk factors for dementia trigger widespread inflammation -- which lead to neurodegeneration, gradual cognitive/memory decline, and eventually (late-onset) dementia. Accordingly, one useful strategy to delay dementia could be based upon nanotargeting drug(s), using lipid nanocarriers, toward a major receptor class responsible for inflammation-associated (cytokine-mediated) cell signaling events. At the same time, the immune response and excessive inflammation, commonly observed in the very recent human coronavirus (COVID-19) pandemic, may accelerate the progression of brain inflammatory neurodegeneration—which increases the probability of post-infection memory impairment and accelerating progression of Alzheimer’s disease. Hence, the proposed multitasking combination therapeutic, using a (biobased) lipid nanocarrier, may also display greater effectiveness at different stages of dementia.