Ikonomovic Milos D, Mufson Elliott J, Wuu Joanne, Cochran Elizabeth J, Bennett David A, DeKosky Steven T
Department of Neurology, University of Pittsburgh School of Medicine, PA 15213, USA.
J Alzheimers Dis. 2003 Feb;5(1):39-48. doi: 10.3233/jad-2003-5106.
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.
最近的几项研究表明，轻度认知障碍（MCI）患者和早期阿尔茨海默病（AD）患者大脑皮质中的胆碱能酶活性得以保留。我们将宗教团体研究中受试者的海马胆碱乙酰转移酶（ChAT）活性水平与AD病变程度进行了关联分析，这些受试者包括无认知障碍（NCI）、MCI以及轻度至中度AD患者。我们还测定了一组纳入匹兹堡大学阿尔茨海默病研究中心的终末期AD患者的海马ChAT活性水平。MCI受试者的特征是海马ChAT活性增加。这种升高在轻度AD病例中不再存在，轻度AD病例与NCI受试者没有差异。重度AD病例显示海马ChAT水平明显降低。在NCI、MCI和轻度至中度AD患者中，海马ChAT活性水平与内嗅皮质和海马中神经炎性斑块病理进展之间存在正相关。在MCI组中，仅在内侧颞叶（即内嗅-海马，Ⅲ/Ⅳ层）Braak分期中发现海马ChAT显著升高。我们推测，MCI受试者海马中的胆碱能变化反映了对内嗅皮质输入丧失导致海马逐渐去神经支配的一种代偿反应。此外，目前的研究结果表明，MCI中观察到的短期记忆丧失不是由胆碱能缺陷引起的；它更可能与内嗅-海马连接中断有关。
