Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease
Superior frontal cortex cholinergic axon density in mild cognitive impairment and early Alzheimer disease
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DOI：
10.1001/archneur.64.9.1312
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发表时间：
2007-09-01
影响因子：
--
通讯作者：
DeKosky, Steven T.
中科院分区：
文献类型：
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作者：
Ikonomovic, Milos D.;Abrahamson, Eric E.;DeKosky, Steven T.
背景：皮质胆碱乙酰转移酶（ChAT）活性的丧失有助于终末期阿尔茨海默病（AD）痴呆。一般而言，ChAT活性水平在轻度至中度AD（mAD）的新皮层中是稳定的，而在轻度认知障碍（MCI）的上级额叶皮层（SFC）中存在选择性上调，表明存在短暂的、区域特异性的胆碱能神经可塑性反应。目的：评估MCI受试者SFC中ChAT活性水平增加是否是胆碱能轴突增殖的基础。设计：体视学原理被应用于评估从没有认知障碍、MCI和mAD的受试者死后获得的SFC组织中ChAT免疫反应纤维和轴突静脉曲张的密度。受试者：36名受试者参加了宗教秩序研究，记录了额叶特异性和整体认知功能的年度临床评估。与无认知功能障碍组相比，MCI组SFC ChAT免疫反应阳性纤维和轴突静脉曲张密度没有改变，但在mAD组显著降低，并与额叶和整体认知功能受损相关。MCI中SFC的胆碱能轴突神经支配缺乏增加，这表明胆碱能谱的结构重组不是本研究中报道的瞬时胆碱能可塑性的机制。地区此外，胆碱能酶活性在mAD中的稳定性可能是ChAT蛋白或SFC中酶活性水平的生化上调的结果，补偿了区域胆碱能纤维和轴突静脉曲张的减少。
Background: Loss of cortical choline acetyltransferase ( ChAT) activity contributes to end-stage Alzheimer disease ( AD) dementia. In general, ChAT activity levels are stable in the neocortex in mild to moderate AD (mAD) and there is a selective up-regulation in the superior frontal cortex (SFC) in mild cognitive impairment (MCI), indicating a transient, region-specific cholinergic neuroplastic response.Objective: To assess whether a proliferation of cholinergic axons underlies increased ChAT activity levels in the SFC in subjects with MCI.Design: Stereologic principles were applied to assess the density of ChAT-immunoreactive fibers and axon varicosities in SFC tissue obtained postmortem from subjects with no cognitive impairment, MCI, and mAD.Subjects: Thirty-six subjects enrolled in the Religious Orders Study, with records of annual clinical evaluation for frontal lobe specific and global cognitive functions.Results: Compared with the group with no cognitive impairment, SFC ChAT-immunoreactive fiber and axon varicosity densities were not altered in the MCI group but were significantly reduced in the group with mAD and correlated with impaired frontal lobe and global cognitive function.Conclusions: The lack of an increase in cholinergic axonal innervation of the SFC in MCI suggests that structural reorganization of cholinergic profiles is not the mechanism underlying the transient cholinergic plasticity reported in this region. Furthermore, the stability of cholinergic enzyme activity in mAD is likely the result of a biochemical up-regulation of ChAT protein or enzyme activity levels in the SFC, compensating for decreased regional cholinergic fibers and axon varicosities.