Regulatory changes in presynaptic cholinergic function assessed in rapid autopsy material from patients with Alzheimer disease: Implications for etiology and therapy

T. A. Slotkin, F. J. Seidler, B. J. Crain, J. M. Bell, G. Bissette, C. B. Nemeroff

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Abstract

Brain regions from patients with or without Alzheimer disease (AD) were obtained within 2 hr of death and examined for indices of presynaptic cholinergic function. Consistent with loss of cholinergic projections, cerebral cortical areas involved in AD exhibited decreased choline acetyltransferase (acetyl-CoA:choline 0-acetyltransferase, EC 2.3.1.6) activity. However, remaining nerve terminals in these regions displayed marked up-regulation of synaptosomal high affinity [3H]choline uptake, a result indicative of relative cholinergic hyperactivity. As choline uptake is also rate-limiting in acetylcholine biosynthesis, these findings have implications for both therapy and identification of causes contributing to neuronal death in AD.

Original languageEnglish (US)
Pages (from-to)2452-2455
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume87
Issue number7
DOIs
StatePublished - Apr 1990

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