The interplay of neurotransmitters in Alzheimer's disease.
Evidence exists for both cholinergic and glutamatergic involvement in the etiology of Alzheimer's disease. Acetylcholine (ACh), a neurotransmitter essential for processing memory and learning, is decreased in both concentration and function in patients with Alzheimer's disease. This deficit and other presynaptic cholinergic deficits, including loss of cholinergic neurons and decreased acetylcholinesterase activity, underscore the cholinergic hypothesis of Alzheimer's disease. The glutamatergic hypothesis links cognitive decline in patients with Alzheimer's to neuronal damage resulting from overactivation of N-methyl-d-aspartate (NMDA) receptors by glutamate. The sustained low-level activation of NMDA receptors, which are pivotal in learning and memory, may result from deficiencies in glutamate reuptake by astroglial cells in the synaptic cleft. This article reviews the roles of ACh and glutamate in Alzheimer's disease, with particular attention given to the overlap between cholinergic and glutamatergic pathways. In addition, the potential synergy between cholinesterase inhibitors and the NMDA receptor antagonist memantine in correcting neurologic abnormalities associated with Alzheimer's disease is addressed.
Francis
Paul T
PT
Wolfson Centre for Age-Related Diseases, GKT School of Biomedical Science at King's College London, Guy's Campus, St. Thomas Street, London SE1 1UL, UK. paul.francis@kcl.ac.uk
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002799:Cholinergic Fibers / Q000378:metabolism / Q000473:pathology; D050491:Glutamate Plasma Membrane Transport Proteins / Q000378:metabolism; D006801:Humans; D009434:Neural Pathways / Q000473:pathology; D018377:Neurotransmitter Agents / Q000378:metabolism / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
D050491:Glutamate Plasma Membrane Transport Proteins; D018377:Neurotransmitter Agents; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate