Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease
Locus coeruleus neurofibrillary degeneration in aging, mild cognitive impairment and early Alzheimer's disease
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DOI：
10.1016/j.neurobiolaging.2006.02.007
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发表时间：
2007-03-01
影响因子：
4.2
通讯作者：
Mesulam, M. Marsel
中科院分区：
文献类型：
--
作者：
Grudzien, Aneta;Shaw, Pamela;Mesulam, M. Marsel
在阿尔茨海默病(AD)的神经病理中，基底核的神经纤维变性及其皮质胆碱能投射的丢失是突出的组成部分。AD脑还与蓝斑核(I-C)发出的去甲肾上腺素能投射退行性改变有关，但这种损害的时间进程尚不清楚。为了确定LC是否在导致AD的早期事件过程中表现出神经纤维异常，我们检查了7名认知正常对照和5名轻度认知损害(MCI)或早期AD的受试者的组织样本。酪氨酸羟化酶免疫组织化学被用来作为LC神经元的标志，而AT8免疫标记显示了与神经原纤维缠结及其前体相关的异常tau。硫黄素-S被用作发育完全的缠结的标记。我们发现在两组标本中都存在AT8阳性标记和硫代拉丁-S阳性缠结。然而，在认知受损组中，包含这些标记的神经元的百分比明显更高。MMSE评分与细胞病理学两项指标均呈负相关。这些结果表明，LC中的细胞病理学是AGE-MCI-AD连续体中的早期事件，它可能是导致痴呆的认知变化出现的众多因素之一。(C)2006 Elsevier Inc.保留所有权利。
Neurofibrillary degeneration in the nucleus basalis and a loss of its cortical cholinergic projections are prominent components of the neuropathology in Alzheimer's disease (AD). The AD brain is also associated with a degeneration of the noradrenergic projections arising from the nucleus locus coeruleus (I-C), but the time course of this lesion is poorly understood. To determine whether the LC displays neurofibrillary abnormalities early in the course of events leading to AD, we examined tissue specimens from seven cognitively normal controls and five subjects at the stages of mild cognitively impairment (MCI) or early AD. Tyrosine hydroxylase immunochemistry was used as a marker of LC neurons while AT8 immunolabeling visualized abnormal tau associated with neurofibrillary tangles and their precursors. Thioflavine-S was used as a marker for fully developed tangles. We found that AT8-positive labeling and thiollavine-S positive tangles were present in both groups of specimens. However, the percentage of neurons containing each of these markers was significantly higher in the cognitively impaired group. The MMSE scores displayed a negative correlation with both markers of cytopathology. These results indicate that cytopathology in the LC is an early event in the age-MCI-AD continuum and that it may be listed among the numerous factors that mediate the emergence of the cognitive changes leading to dementia. (c) 2006 Elsevier Inc. All rights reserved.