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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 bindings 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. |
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