Acetylcholinergic neurotransmission and the beta-amyloid cascade: implications for Alzheimer's disease.
Alzheimer's disease is characterized by both decreases in acetylcholinergic neurotransmission and increases in beta-amyloid accumulation. Currently, available clinical psychopharmacologic treatment is focused on increasing acetylcholinergic neurotransmission, whereas no clinical treatments to directly reduce beta-amyloid accumulation are available. Cholinesterase inhibitors improve cognition, certain neuropsychiatric symptoms and functional impairment in patients with mild-to-moderate Alzheimer's disease, and it is believed that this is mainly symptomatic treatment. However, this review discusses various levels of interaction between acetylcholinergic neurotransmission and the beta-amyloid cascade, which suggest that some specific acetylcholinergic treatments may reduce beta-amyloid accumulation, and therefore may slow disease progression over the long term. Various suggestions are made on how such potential disease-modifying effects could be studied in the future.
Verhoeff
Nicolaas Paul L G
NP
Department of Psychiatry, Faculty of Medicine, University of Toronto, Canada. pverhoeff@klaru-baycrest.on.ca
D000109:Acetylcholine / Q000378:metabolism*; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D005104:Expert Testimony; D006801:Humans; D058225:Plaque, Amyloid / Q000187:drug effects / Q000378:metabolism; D043643:Receptor, Muscarinic M1 / Q000037:antagonists & inhibitors / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology; D064569:alpha7 Nicotinic Acetylcholine Receptor
D016229:Amyloid beta-Peptides; D014150:Antipsychotic Agents; D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; D043643:Receptor, Muscarinic M1; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D000109:Acetylcholine