title: Does Anticholinergic Activity Affect Neuropathology? Implication of Neuroinflammation in Alzheimer's Disease.
abstract: One characteristic neuropathological feature of Alzheimer's disease (AD) is profound neuronal loss in the nucleus basalis of Meynert, the major source of cholinergic innervation of the cerebral cortex. Clinically, anticholinergic activity causes a decline in cognitive function and increases the risk of dementia, thus possibly enhancing AD pathologies and neurodegeneration. Until now there has been insufficient human neuropathological data to support this conclusion. Experimental studies using a tauopathy mouse model demonstrated anticholinergics enhanced tau pathology and neurodegeneration corresponding to central anticholinergic activity. Additionally, donepezil, a cholinesterase inhibitor, ameliorated tau pathology and neurodegeneration in the same mouse model. These results indicate the balance between cholinergic and anticholinergic activities might affect neurodegeneration. Importantly, neurodegeneration observed in the mouse model seemed to correspond to the distribution of microglial activation, and it was reported that neuroinflammation plays an important role in the pathomechanism of AD, while anticholinergic activity augments inflammatory responses. Moreover, some studies indicated β-amyloid itself depletes cholinergic function similarly to anticholinergic activity. Thus, anticholinergic activity might initiate and/or accelerate AD pathology. Limited human data support the conclusion that anticholinergic activity enhances AD-related neuropathology and neurodegeneration. However, experimental data from a tauopathy mouse model indicated anticholinergic activity might enhance neurodegeneration with enhanced neuroinflammation including microglial activation.
authors.affiliation: Department of Neurology, Chiba-East National Hospital, Chiba, Japan.
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Yoshiyama
authors.forename: Ayako
authors.initials: A
authors.lastname: Kojima
authors.forename: Kimiko
authors.initials: K
authors.lastname: Itoh
authors.forename: Sagiri
authors.initials: S
authors.lastname: Isose
authors.forename: Mizuho
authors.initials: M
authors.lastname: Koide
authors.forename: Koji
authors.initials: K
authors.lastname: Hori
authors.forename: Kimihito
authors.initials: K
authors.lastname: Arai
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004660:Encephalitis / Q000209:etiology*; D006801:Humans; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D018680:Cholinergic Antagonists; D016875:tau Proteins; D000109:Acetylcholine