Involvement of Nutrients in the Pathogenesis or Management of Alzheimer’s Disease

Abstract

The number of hippocampal and cortical synapses is diminished in early Alzheimer’s disease (AD) and this loss, which is well correlated with the onset of cognitive deficits, probably reflects both an acceleration in their breakdown and a slowing in their synthesis, perhaps consequent to the concurrent decrease in dendritic spines. No strategies have been identified for increasing the number of synapses. Synaptogenesis requires adequate amounts of highly specialized synaptic membrane and activation of a process for shaping this membrane, initially into dendritic spines and neurites and then into the synapses themselves. Both can be enhanced by providing, concurrently, three circulating compounds present in the diet—uridine (as its monophosphate), docosahexaenoic acid (DHA), and choline—which can be rate-limiting precursors in membrane phosphatide synthesis. The uridine, as uridine triphosphate (UTP), also activates brain P2Y receptors, which facilitate neuronal differentiation and affect the production of synaptic proteins. In two large-scale clinical trials, patients with early AD who received the precursors and cofactors orally for up to 24 weeks exhibited significant improvements in memory indices.