Busser J, Geldmacher D S, Herrup K
Alzheimer Research Laboratory, Department of Neurology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106, USA.
J Neurosci. 1998 Apr 15;18(8):2801-7. doi: 10.1523/JNEUROSCI.18-08-02801.1998.
Alzheimer's disease (AD) is a major dementing illness characterized by regional concentrations of senile plaques, neurofibrillary tangles, and extensive neuronal cell death. Although cell and synaptic loss is most directly linked to the severity of symptoms, the mechanisms leading to the neuronal death remain unclear. Based on evidence linking neuronal death during development to unexpected reappearance of cell cycle events, we investigated the brains of 12 neuropathologically verified cases of Alzheimer's disease and eight age-matched, disease-free controls for the presence of cell cycle proteins. Aberrant expression of cyclin D, cdk4, proliferating cell nuclear antigen, and cyclin B1 were identified in the hippocampus, subiculum, locus coeruleus, and dorsal raphe nuclei, but not inferotemporal cortex or cerebellum of AD cases. With only one exception, control subjects showed no significant expression of cell cycle markers in any of the six regions. We propose that disregulation of various components of the cell cycle is a significant contributor to regionally specific neuronal death in AD.
阿尔茨海默病（AD）是一种主要的痴呆症，其特征为老年斑、神经原纤维缠结的区域聚集以及广泛的神经元细胞死亡。尽管细胞和突触的丧失与症状的严重程度最为直接相关，但导致神经元死亡的机制仍不清楚。基于将发育过程中的神经元死亡与细胞周期事件意外重现联系起来的证据，我们研究了12例经神经病理学证实的阿尔茨海默病病例以及8例年龄匹配的无病对照者的大脑中细胞周期蛋白的存在情况。在AD病例的海马体、下托、蓝斑和中缝背核中发现了细胞周期蛋白D、细胞周期蛋白依赖性激酶4、增殖细胞核抗原和细胞周期蛋白B1的异常表达，但在颞下回皮质或小脑中未发现。除了一个例外，对照者在这六个区域中的任何一个区域均未显示出细胞周期标志物的显著表达。我们提出，细胞周期各组成部分的失调是AD中区域特异性神经元死亡的一个重要因素。
