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Article type: Research Article
Authors: Ikonomovic, Milos D.a; b | Mufson, Elliott J.c | Wuu, Joannec | Cochran, Elizabeth J.c | Bennett, David A.c | DeKosky, Steven T.a; b; *
Affiliations: [a] Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA | [b] Psychiatry, and Alzheimer's Disease Research Center, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA | [c] Department of Neurological Sciences and Rush Alzheimer's Disease Center, Rush Presbyterian-St. Luke's Medical Center, Chicago IL, 60612, USA
Correspondence: [*] Corresponding author: Steven T. DeKosky, M.D., Alzheimer's Disease Research Center, University of Pittsburgh Medical Center, MUH 4th Floor, 200 Lothrop Street, Pittsburgh, PA 15213, USA. Tel.: +1 412 6246889; Fax: +1 412 6247814; E-mail: dekoskyst@upmc.edu.
Abstract: Several recent studies indicate that activity of cholinergic enzymes in the cortex of people with mild cognitive impairment (MCI) and early Alzheimer's disease (AD) are preserved. We correlated levels of hippocampal choline acetyltransferase (ChAT) activity with the extent of AD lesions in subjects from the Religious Order Study, including cases with no cognitive impairment (NCI), MCI, and with mild to moderate AD. Hippocampal ChAT activity levels were also determined in a group of end-stage AD patients who were enrolled in the University of Pittsburgh Alzheimer's Disease Research Center. MCI subjects were characterized with increased hippocampal ChAT activity. This elevation was no longer present in mild AD cases, which were not different from NCI subjects. Severe AD cases showed markedly depleted hippocampal ChAT levels. In NCI, MCI, and mild-moderate AD, there was a positive correlation between hippocampal ChAT activity levels and progression of neuritic plaque pathology in entorhinal cortex and hippocampus. A significant elevation of hippocampal ChAT in the MCI group was found selectively in the limbic (i.e., entorhinal-hippocampal, III/IV) Braak stages. We hypothesize that cholinergic changes in the hippocampus of MCI subjects reflect a compensatory response to the progressive denervation of the hippocampus by lost entorhinal cortex input. Moreover, the present findings suggest that the short-term memory loss observed in MCI is not caused by cholinergic deficits; it more likely relates to disrupted entorhinal-hippocampal connectivity.
DOI: 10.3233/JAD-2003-5106
Journal: Journal of Alzheimer's Disease, vol. 5, no. 1, pp. 39-48, 2003
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