title: Altered synaptic function in Alzheimer's disease.
abstract: Alzheimer's disease is the leading cause of dementia in the elderly, presenting itself clinically by progressive loss of memory and learning. Since synaptic density correlates more closely with cognitive impairment than any other pathological lesion observable in the disease pathology, an increased understanding of the mechanisms behind synaptic disconnection is of vital importance. Our lab investigated the neurotransmitter-specific status of distinct cortical presynaptic bouton populations in various transgenic mouse models of the Alzheimer's-like amyloid pathology in order to assess their involvement throughout the progression of the pathology. These studies have revealed that the amyloid pathology appears to progress in a neurotransmitter-specific manner where the cholinergic terminals appear most vulnerable, followed by the glutamatergic terminals and finally by the somewhat more resilient GABAergic terminals. This review will discuss additional studies which also provide evidence of a neurotransmitter-specific pathology as well as comment on the potential explanations for the observed vulnerabilities, touching upon metabolic demand, trophic support and receptor mediated activation.
authors.affiliation: Department of Pharmacology and Therapeutics, McGill University, 3655 Sir William Osler Promenade, Montreal, QC, Canada H3G 1Y6.
authors.forename: Karen F S
authors.initials: KF
authors.lastname: Bell
authors.forename: A
authors.initials: A
authors.lastname: Claudio Cuello
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000502:physiology; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008559:Memantine / Q000627:therapeutic use; D051379:Mice; D008822:Mice, Transgenic; D016501:Neurites / Q000502:physiology; D018377:Neurotransmitter Agents / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013569:Synapses / Q000502:physiology*
chemical_list: D016229:Amyloid beta-Peptides; D018377:Neurotransmitter Agents; D016194:Receptors, N-Methyl-D-Aspartate; D008559:Memantine