Muscarinic Binding and Choline Acetyltransferase in Postmortem Brains of Demented Patients

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Abstract
Postmortem human brain samples were taken from non-neurological controls as well as demented subjects who died with Alzheimer's disease (AD), multi-infarct dementia (MID), or a combination of AD and MID dementia (MIXED). Choline acetyltransferase (Ch AT) activity was measured radiometrically using [ 1 -l4C]acetyl-coenzyme A as the substrate, muscarinic binding was assayed with [3H]quinuclidinyl benzilate, and the proportion of binding associated with high affinity agonist sites was measured by carbamylcholine displacement of the radioligand.Relative to control, ChAT activity was significantly reduced (p ≤0.01) in samples taken from the temporal, frontal, and hippocampal areas of demented patients. A small elevation in Bmax was noted in the hippocampal endplate (p ≤0.01) (AD vs. control) and the H1-subiculum region (p ≤0.05) (AD vs. all other groups). In addition, the percentage of binding associated with high affinity agonist sites was greater in the frontal cortex of AD and MID samples (p≤0.05), compared with MIXED and control, and in the temporal cortex of the AD group compared with all other groups (p≤0.05). The results suggest a regionally specific upregulation of cerebral muscarinic receptors in dementia, especially in AD.