Challenging the Cholinergic Hypothesis in Alzheimer Disease
- 21 April 1999
- journal article
- editorial
- Published by American Medical Association (AMA) in Jama-Journal Of The American Medical Association
- Vol. 281 (15), 1433-1434
- https://doi.org/10.1001/jama.281.15.1433
Abstract
The idea that some of the symptoms of Alzheimer disease are due to a deficiency of the neurotransmitter acetylcholine in the brain first surfaced in 1976 and 1977.1-3 Several groups of investigators reported that the activity of enzymes involved in the synthesis (choline acetyltransferase [ChAT]) and degradation (acetylcholinesterase [AChE]) of acetylcholine were markedly reduced in activity in autopsy brain tissue from patients with end-stage Alzheimer disease, and many subsequent studies have confirmed these findings. A few groups have reported deficits in ChAT activity or acetylcholine release in biopsy tissue from living patients with Alzheimer disease4 and several reports have shown that the extent of the deficits in autopsy brain tissue correlate with the severity of the disease (as determined by the density of neuritic plaques, neurofibrillary tangles, or both). The cholinergic hypothesis5 of Alzheimer disease that evolved from these studies simply postulates that at least some of the cognitive decline experienced by patients with Alzheimer disease results from a deficiency of acetylcholine, or cholinergic neurotransmission. This hypothesis has been the stimulus for a great deal of effort in experimental pharmacology and a large number of clinical trials.This publication has 8 references indexed in Scilit:
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- NECROPSY EVIDENCE OF CENTRAL CHOLINERGIC DEFICITS IN SENILE DEMENTIAThe Lancet, 1977
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