Alzheimer’s disease – because β-amyloid cannot distinguish neurons from bacteria: an in silico simulation study

Based on semi-empirical quantum mechanics calculations and extensive molecular mechanics calculations and molecular dynamics simulations, a novel molecular level conceptualization of key biochemical events in the pathogenesis of Alzheimer’s disease (AD) is presented. In response to immune stimulating events ( e.g ., infection, trauma), β-amyloid (Aβ) protein is released in brain as a protective immunopeptide triggering an immunity cascade in which Aβ exhibits antimicrobial activity, which mistakenly results in a misdirected attack upon “self” neurons, arising from the macromolecular and electrochemical similarities between neurons and bacteria in terms of transmembrane potential gradients and anionic charge distribution geometries on outer membrane macromolecules (gangliosides in neurons; cardiolipins or lipopolysaccharides in bacteria). Molecular mechanics/dynamics calculations are used to demonstrate how the inability of Aβ to distinguish between bacteria and neurons is a central pathological process in the pathogenesis of AD.