Author Affiliation: Albert Einstein College of Medicine, Bronx, NY.
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
Davies P. Challenging the Cholinergic Hypothesis in Alzheimer Disease. JAMA. 1999;281(15):1433–1434. doi:10.1001/jama.281.15.1433
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