Nicotinic binding sites in cerebral cortex and hippocampus in Alzheimer's dementia.
Postmortem cerebral neocortical and hippocampal samples were taken from patients who died with dementia of the Alzheimer type (DAT) and individuals without diagnoses of neurological or psychiatric disease (control). Nicotinic binding was assayed with 20 nM [3H]acetylcholine [( 3H]ACh) in the presence of atropine, or with 4 nM (-)-[3H]nicotine ((-)-[3H]Nic). Binding of both ligands was lower in the following regions from DAT vs. control brains (P less than or equal to 0.05): superior, middle and inferior temporal gyri, orbital frontal gyrus, middle frontal gyrus, pre- and postcentral gyri, inferior parietal lobule, and hippocampal endplate. Values of the correlation coefficient (r's) for binding of the nicotinic cholinergic ligands in these regions ranged from 0.70 to 0.93 (P's less than 0.05), suggesting that [3H]ACh and (-)-[3H]Nic labeled the same sites in human brain. There was no difference in nicotinic binding in the presubiculum, comparing DAT and control samples (P greater than 0.05). Here too, correlations between binding of the two ligands were statistically significant in control and DAT groups (r's = 0.92, P's less than 0.05). Nicotinic binding measured with [3H]ACh, but not (-)-[3H]Nic, was significantly lower in the H2 (field of Rose) and H1-subiculum areas of DAT samples compared to control. Correlations between binding of the two ligands in these regions ranged from 0.21 to 0.34 for the two groups (P's greater than 0.05). The findings support a loss of neocortical and hippocampal nicotinic cholinergic binding sites in DAT.(ABSTRACT TRUNCATED AT 250 WORDS)
London
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ED
Neuropharmacology Laboratory, National Institute on Drug Abuse, Baltimore, MD 21224.
Ball
M J
MJ
Waller
S B
SB
D000109:Acetylcholine; D000544:Alzheimer Disease / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D006624:Hippocampus / Q000378:metabolism*; D006801:Humans; D008297:Male; D009538:Nicotine; D011869:Radioligand Assay; D011978:Receptors, Nicotinic / Q000378:metabolism*
D011978:Receptors, Nicotinic; D009538:Nicotine; D000109:Acetylcholine