Galanin is a recently isolated
neuropeptide that is of particular interest in dementing disorders because of its known colocalization with
choline acetyltransferase in magnocellular neurons of the basal nucleus of Meynert. These neurons degenerate in
Alzheimer's disease, and there is a corresponding deficiency of cortical
choline acetyltransferase activity. In the present study,
galanin-like immunoreactivity was measured in the postmortem cerebral cortex and hippocampus of 10 controls and 14 patients who had had
Alzheimer's disease. Significant reductions of
choline acetyltransferase activity (50-60%) were found in all regions examined; however, there was no significant effect on concentrations of
galanin-like immunoreactivity. Similar measurements were made in postmortem tissues of 12 control and 13 demented Parkinsonian patients who had had Alzheimer-type cortical pathology.
Choline acetyltransferase activity was again significantly decreased in all regions examined but there were no significant reductions in
galanin-like immunoreactivity. Experimental lesions of the fornix in rats produced parallel significantly correlated reductions of both
choline acetyltransferase activity and
galanin-like immunoreactivity in the hippocampus.
Galanin-like immunoreactivity in the human hypothalamus consisted of two molecular-weight species on gel-permeation chromatography, and two forms were resolved by reverse-phase HPLC. The paradoxical preservation of
galanin-like immunoreactivity, despite depletion of the activity of
choline acetyltransferase, with which it is colocalized, is as yet unexplained. Recent studies have shown that
galanin inhibits both
acetylcholine release in the hippocampus and memory acquisition; therefore, preserved
galanin may exacerbate the
cholinergic and cognitive deficits that accompany
dementia.