The role of D-amino acids in neurodegeneration associated with Alzheimer’s disease

Alzheimer’s disease is the most common neurodegenerative disease, characterized by deposits of amyloid beta and tau protein in the brain. D-amino acids, primarily represented in the central nervous system by D-serine, play a key role in modulating synaptic transmission. Normally, D-serine, synthesized in neurons and glial cells, facilitates glutamatergic transmission and provides a trophic effect in neural networks. Aging is accompanied by a decrease in D-serine synthesis leading to reduced NMDA receptor activity, a decline in the magnitude of long-term potentiation in the hippocampus, and a weakening of neural plasticity. The complex pathogenetic changes in Alzheimer’s disease, represented by microglial senescence and neuroinflammation, promote the synthesis of additional amounts of D-serine, which cause both excitotoxicity due to excessive stimulation of NMDA receptors, and neurodegeneration processes that trigger dementia. This paper presents data on the relationship between glial dysfunction, excitotoxicity, and neurodegeneration with D-amino acid metabolism and discusses the potential of using D-amino acids to diagnose Alzheimer’s disease. Keywords: D-serine, D-amino acids, NMDA receptors, microglial senescence, neuroinflammation, neurodegeneration, Alzheimer’s disease