Does Anticholinergic Activity Affect Neuropathology? Implication of Neuroinflammation in Alzheimer's Disease.

Does Anticholinergic Activity Affect Neuropathology? Implication of Neuroinflammation in Alzheimer's Disease.
Neurodegener Dis. 2015;15(3):140-8
Authors: Yoshiyama Y, Kojima A, Itoh K, Isose S, Koide M, Hori K, Arai K
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 d...

Source: Neuro-Degenerative Diseases - July 5, 2015 Category: Neurology Authors: Yoshiyama Y, Kojima A, Itoh K, Isose S, Koide M, Hori K, Arai K Tags: Neurodegener Dis Source Type: research