Alzheimer’s disease, oxidative stress and B-vitamin depletion

Abstract

There is an association between cognitive function and vitamin B12 and folate status. Both vitamins participate in recycling the potentially toxic amino acid homocysteine to methionine and, ultimately, to the methyl donor S-adenosylmethionine (SAM). Consequently, B12 and folate indirectly influence glutathione synthesis – a major intracellular antioxidant. Neuroinflammation and oxidative stress are early features of Alzheimer’s disease (AD). Such stress impairs homocysteine recycling, degrades folate and decreases its cellular retention, resulting in limited SAM availability and increased homocysteine levels. Oxidized homocysteine derivatives, such as homocysteic acid, can initiate a vicious cycle by promoting free-radical formation. Decreased SAM also fosters development of characteristic AD neuropathologies – neurofibrillary tangles and amyloid plaques. The latter generate additional free radicals in a further feed-forward cascade. Future therapies should simultaneously halt neuroinflammation, restore redox homeostasis and replace depleted intracellular B vitamins. Developing early markers for these harmful processes will allow targeting of such therapy before irreversible cellular damage ensues.