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Anatomy of cholinesterase inhibition in Alzheimer's disease: Effect of physostigmine and tetrahydroaminoacridine on plaques and tangles
Author(s) -
Mesulam M.Marsel,
Geula Changiz,
Asuncion Morán M.
Publication year - 1987
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410220603
Subject(s) - physostigmine , cholinesterase , acetylcholinesterase , alzheimer's disease , senile plaques , butyrylcholinesterase , cerebral cortex , cholinergic , neocortex , acetylcholine , medicine , neuroscience , endocrinology , chemistry , pathology , aché , psychology , disease , enzyme , biochemistry
Abstract The histochemical distribution of cholinesterases in the cerebral cortex and their response to cholinesterase inhibitors such as physostigmine and tetrahydroaminoacridine (THA) were investigated in brains from patients with Alzheimer's disease and control subjects. In the temporal neocortex of the control subjects, most of the cholinesterase activity was located within axons and cell bodies belonging to cholinergic pathways. In keeping with their well‐known cholinomimetic effects, physostigmine and THA effectively inhibited this cholinesterase activity. Cholinesterase‐containing normal axons (and in some cases cells) were severely depleted in the cerebral cortex of patients with Alzheimer's disease. Although the cerebral cortex of these patients continued to display abundant cholinesterase activity, the location of this enzyme was largely shifted to the neuritic plaques and neurofibrillary tangles. In fact, the majority of these pathological structures demonstrated intense acetylcholinesterase and butyrylcholinesterase activities. Physostigmine and THA were potent inhibitors of these plaque‐ and tangle‐bound cholinesterases as well. In patients with Alzheimer's disease, cholinesterase inhibitors would therefore appear to have a major and widespread effect directly upon the enzymatic activity of plaques and tangles. Consequently, the clinical effects of anticholinesterases in Alzheimer's disease may be based on mechanisms that are different from those that apply to the normal brain.