Cortical biopsy in Alzheimer's disease: Diagnostic accuracy and neurochemical, neuropathological, and cognitive correlations

Neurochemical assessments were performed on biopsy samples taken from the right frontal lobe of patients diagnosed with Alzheimer's disease (AD), before the implantation of a ventricular catheter and pump assembly for the infusion of bethanechol chloride as an experimental therapy. The pathologically diagnosed patients with AD (n = 35; mean age, 67 ± 1.5 yr) were compared with a group of samples from normal age‐equivalent autopsied controls (n = 22; mean age, 68 ± 2 yr) and autopsied AD brains (n = 11; mean age, 73 ± 2 yr). Samples were assayed for choline acetyltransferase (ChAT), acetylcholinesterase, binding to {³H}quinuclidinyl benzilate as an index of total muscarinic cholinergic binding, and [³H}pirenzepine binding as an index of Ml cholinergic receptor subtype binding. Mean levels of ChAT activity were decreased in the biopsied patients to 36% of age‐matched autopsied controls. The loss of ChAT activity correlated significantly with the Mini‐Mental State Examination, an index of global cognitive function. Mean ChAT activity in autopsied AD cortex was further decreased compared with controls, indicating continuous decline through the course of the disease. Acetylcholinesterase followed a similar, less dramatic decline. No differences were found in {³H}quinuclidinyl benzilate binding or {³H}pirenzepine binding between biopsied and autopsied controls. Neuritic plaque counts did not correlate with either the Mini‐Mental State Examination or ChAT activity in the biopsy specimens. The correlation of cortical ChAT activity with degree of dementia, although considerably weaker than those of cortical synaptic density with dementia, is the first demonstration of such a relationship in biopsied patients, and suggests another reason why the AD brain may be unresponsive to presynaptic cholinergic manipulations or attempts at enhancement.