Memantine administration enhances glutamatergic and GABAergic pathways in human hippocampus of Alzeimer´s disease patients

Alzheimer´s disease (AD) represents a serious health, social and economic problem. One of the traditional treatment is administration of memantine, the NMDA receptor antagonist. In this study we investigated how memantine medication impacts protein expression in hippocampus of AD patients using TMT-based quantitative proteomics applied on formalin-fixed paraffin embedded post mortem tissues. The presented dataset shows that memantine treatment has minor but distinct effect on protein expression. While memantine did not prevented general decline of mitochondrial proteome seen in unmedicated AD patients, the treatment selectively induced levels of several mitochondrially-encoded proteins. Furthermore, memantine medication mitigated proteomic pattern of activated phagocytes and enhanced expression of synaptic components involved in both inhibitory (GABA) and excitatory (glutamate) neurotransmission. The upregulation was specific for proteins for which glutamate/GABA serves as a ligand or a substrate (i.e. receptors, transporters, enzymes, etc.), without affecting neuronal nor post-synaptic density markers. This may indicate that memantine-associated effects on glutamatergic and GABAergic is a reaction to memantine-mediated changes of glutamate and GABA levels.