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阿尔茨海默病患者基底前脑胆碱能神经元变性的异质性和选择性。

Heterogeneity and selectivity of the degeneration of cholinergic neurons in the basal forebrain of patients with Alzheimer's disease.

作者信息

Lehéricy S, Hirsch E C, Cervera-Piérot P, Hersh L B, Bakchine S, Piette F, Duyckaerts C, Hauw J J, Javoy-Agid F, Agid Y

机构信息

INSERM U.289, Bâtiment Nouvelle Pharmacie, Paris, France.

出版信息

J Comp Neurol. 1993 Apr 1;330(1):15-31. doi: 10.1002/cne.903300103.

DOI:10.1002/cne.903300103
PMID:8468401
Abstract

Cholinergic neurons were studied by immunohistochemistry, with an antiserum against choline acetyltransferase (ChAT), in the basal forebrain (Ch1 to Ch4) of four patients with Alzheimer's disease (AD) and four control subjects. ChAT-positive cell bodies were mapped and counted in Ch1 (medial septal nucleus), Ch2 (vertical nucleus of the diagonal band), Ch3 (horizontal nucleus of the diagonal band) and Ch4 (nucleus basalis of Meynert). Compared to controls, the number of cholinergic neurons in AD patients was reduced by 50% on average. The interindividual variations in cholinergic cell loss were high, neuronal loss ranging from moderate (27%) to severe (63%). Despite the small number of brains studied, a significant correlation was found between the cholinergic cell loss and the degree of intellectual impairment. To determine the selectivity of cholinergic neuronal loss in the basal forebrain of AD patients, NPY-immunoreactive neurons were also investigated. The number of NPY-positive cell bodies was the same in controls and AD patients. The results (1) confirm cholinergic neuron degeneration in the basal forebrain in AD and the relative sparing of these neurons in some patients, (2) indicate that degeneration of cholinergic neurons in the basal forebrain contributes to intellectual decline, and (3) show that, in AD, such cholinergic cell loss is selective, since NPY-positive neurons are preserved in the basal forebrain.

摘要

采用抗胆碱乙酰转移酶(ChAT)抗血清,通过免疫组织化学方法对4例阿尔茨海默病(AD)患者和4例对照者的基底前脑(Ch1至Ch4)中的胆碱能神经元进行了研究。对Ch1(内侧隔核)、Ch2(斜角带垂直核)、Ch3(斜角带水平核)和Ch4(Meynert基底核)中的ChAT阳性细胞体进行了定位和计数。与对照组相比,AD患者的胆碱能神经元数量平均减少了50%。胆碱能细胞丢失的个体间差异很大,神经元丢失范围从中度(27%)到重度(63%)。尽管研究的脑标本数量较少,但胆碱能细胞丢失与智力损害程度之间存在显著相关性。为了确定AD患者基底前脑胆碱能神经元丢失的选择性,还对NPY免疫反应性神经元进行了研究。对照组和AD患者中NPY阳性细胞体的数量相同。结果(1)证实了AD患者基底前脑胆碱能神经元的变性以及部分患者中这些神经元相对保留,(2)表明基底前脑胆碱能神经元的变性导致智力衰退,(3)表明在AD中,这种胆碱能细胞丢失是选择性的,因为基底前脑中NPY阳性神经元得以保留。

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