A Fundamental Role for Oxidants and Intracellular Calcium Signals in Alzheimer’s Pathogenesis—And How a Comprehensive Antioxidant Strategy May Aid Prevention of This Disorder

Abstract

Oxidative stress and increased cytoplasmic calcium are key mediators of the detrimental effects on neuronal function and survival in Alzheimer’s disease (AD). Pathways whereby these perturbations arise, and then prevent dendritic spine formation, promote tau hyperphosphorylation, further amplify amyloid β generation, and induce neuronal apoptosis, are described. A comprehensive program of nutraceutical supplementation, comprised of the NADPH oxidase inhibitor phycocyanobilin, phase two inducers, the mitochondrial antioxidant astaxanthin, and the glutathione precursor N-acetylcysteine, may have important potential for antagonizing the toxic effects of amyloid β on neurons and thereby aiding prevention of AD. Moreover, nutraceutical antioxidant strategies may oppose the adverse impact of amyloid β oligomers on astrocyte clearance of glutamate, and on the ability of brain capillaries to export amyloid β monomers/oligomers from the brain. Antioxidants, docosahexaenoic acid (DHA), and vitamin D, have potential for suppressing microglial production of interleukin-1β, which potentiates the neurotoxicity of amyloid β. Epidemiology suggests that a health-promoting lifestyle, incorporating a prudent diet, regular vigorous exercise, and other feasible measures, can cut the high risk for AD among the elderly by up to 60%. Conceivably, complementing such lifestyle measures with long-term adherence to the sort of nutraceutical regimen outlined here may drive down risk for AD even further.