Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, CA 92037, USA.
Neurodegener Dis. 2009;6(5-6):221-9. doi: 10.1159/000236901. Epub 2009 Sep 9.
Alzheimer's disease (AD) is characterized by extensive neuronal death in distinct brain regions, including the frontal cortex and hippocampus, although the specific mechanisms of neuronal degeneration in AD remain a topic of intense scientific pursuit. One model for cell death in AD postulates that abortive cell cycle events in neurons, including tetraploidy, precede neuronal death, and novel therapeutics based on suppressing cell cycle re-entry are being pursued. Using DNA content fluorescence-activated cell sorting combined with fluorescence in situ hybridization and immunostaining, we analyzed neuronal nuclei from postmortem human brain samples from the frontal cortex and hippocampus of nondiseased and AD patients for evidence of tetraploidy. Here, we show that tetraploid nuclei are similarly prevalent in AD and control brains and are exclusively non-neuronal, contrasting with an absence of tetraploid neurons. Our findings demonstrate that neuronal tetraploidy is nonexistent in the AD brain and intimate a reevaluation of neuronal cell cycle re-entry as a therapeutic target for AD.
阿尔茨海默病（AD）的特征是在特定脑区（包括额叶皮质和海马体）广泛存在神经元死亡，尽管 AD 中神经元变性的确切机制仍是科学研究的热点。AD 中细胞死亡的一个模型假设神经元中细胞周期事件的失败，包括四倍体，先于神经元死亡，并且正在追求基于抑制细胞周期再进入的新型治疗方法。我们使用 DNA 含量荧光激活细胞分选结合荧光原位杂交和免疫染色，分析了来自非病变和 AD 患者的额叶皮质和海马体的死后人脑样本中的神经元核，以寻找四倍体的证据。在这里，我们表明四倍体核在 AD 和对照脑中同样普遍存在，并且仅是非神经元，与不存在四倍体神经元形成对比。我们的研究结果表明，AD 脑中不存在神经元四倍体，提示需要重新评估神经元细胞周期再进入作为 AD 的治疗靶点。
