Alzheimer's disease and the basal forebrain cholinergic system: relations to beta-amyloid peptides, cognition, and treatment strategies.
Alzheimer's disease (AD) is the most common form of degenerative dementia and is characterized by progressive impairment in cognitive function during mid- to late-adult life. Brains from AD patients show several distinct neuropathological features, including extracellular beta-amyloid-containing plaques, intracellular neurofibrillary tangles composed of abnormally phosphorylated tau, and degeneration of cholinergic neurons of the basal forebrain. In this review, we will present evidence implicating involvement of the basal forebrain cholinergic system in AD pathogenesis and its accompanying cognitive deficits. We will initially discuss recent results indicating a link between cholinergic mechanisms and the pathogenic events that characterize AD, notably amyloid-beta peptides. Following this, animal models of dementia will be discussed in light of the relationship between basal forebrain cholinergic hypofunction and cognitive impairments in AD. Finally, past, present, and future treatment strategies aimed at alleviating the cognitive symptomatology of AD by improving basal forebrain cholinergic function will be addressed.
Auld
Daniel S
DS
Douglas Hospital Research Centre, 6875 Blvd Lasalle, Verdun, Que, Canada H4H 1R3.
Kornecook
Tom J
TJ
Bastianetto
Stéphane
S
Quirion
Rémi
R
D000109:Acetylcholine / Q000378:metabolism*; D000344:Afferent Pathways / Q000503:physiopathology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology* / Q000601:surgery / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D016380:Brain Tissue Transplantation; D002799:Cholinergic Fibers / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D003072:Cognition Disorders / Q000503:physiopathology / Q000628:therapy; D004195:Disease Models, Animal; D016332:Fetal Tissue Transplantation; D015316:Genetic Therapy; D006801:Humans; D017774:Long-Term Potentiation; D009414:Nerve Growth Factors / Q000378:metabolism / Q000627:therapeutic use; D009474:Neurons / Q000378:metabolism; D016548:Prosencephalon / Q000378:metabolism / Q000503:physiopathology; D011976:Receptors, Muscarinic / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism
D016229:Amyloid beta-Peptides; D002800:Cholinesterase Inhibitors; D009414:Nerve Growth Factors; D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D000109:Acetylcholine