Muscarinic Binding and Choline Acetyltransferase in Postmortem Brains of Demented Patients

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 (ChAT) activity was measured radiometrically using [1-14C]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 less than or equal to 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 less than or equal to 0.01) (AD vs. control) and the H1-subiculum region (p less than or equal to 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 less than or equal to 0.05). The results suggest a regionally specific upregulation of cerebral muscarinic receptors in dementia, especially in AD.