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首页> 外文OA文献 >A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort
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A neuronal DNA damage response is detected at the earliest stages of Alzheimer's neuropathology and correlates with cognitive impairment in the Medical Research Council's Cognitive Function and Ageing Study ageing brain cohort

机译：在阿尔茨海默氏症的神经病理学的早期阶段检测到神经元DNa损伤反应，并与医学研究委员会的认知功能和衰老研究老化脑群中的认知障碍相关联。

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AimsudPopulation-based studies have shown that approximately 20% of the ageing population (aged 65 years and over) with dementia have little or no classical Alzheimer-type neuropathology. Cumulative DNA damage and a reduced capacity of DNA repair may result in neuronal dysfunction and contribute to cognitive impairment independent of Alzheimer-type pathology in the ageing brain.ududMethodsudWe investigated expression of the DNA damage response (DDR)-associated molecules γH2AX and DNA-PKcs using immunohistochemistry and western blotting, and senescence-associated β-galactosidase in the frontal association neocortex of cases with low levels of Alzheimer-type pathology (Braak & Braak stage 0–II), and explored their relationship to cognitive impairment in a population-representative sample from the Medical Research Council's Cognitive Function and Ageing Study cohort.ududResultsudIncreases in both γH2AX+ (rs = −0.36, P = 0.025) and DNA-PKcs+ (rs = −0.39, P = 0.01) neuronal counts were associated with a lower Mini-Mental State Examination score. Increasing levels of senescence associated-β-gal+ pyramidal neurones were weakly associated with the total number of DNA-PKcs+ neurones (P = 0.08), but not with traditional senescence-associated signalling molecules, including p53 and p16.ududConclusionudThe association between the neuronal DDR and cognitive impairment, independent of AD pathology in the ageing brain, may be suggestive of a causal link via neuronal dysfunction.
机译：基于目标人群的研究表明，约20％的老年痴呆症患者（65岁及以上）几乎没有或没有经典的阿尔茨海默氏病类型的神经病理学。 DNA累积损伤和DNA修复能力降低可能会导致神经元功能异常，并导致衰老的大脑中与Alzheimer型病理无关的认知障碍。 ud udMethods ud我们研究了与DNA损伤反应（DDR）相关的分子的表达阿尔茨海默病类型低的病例（Braak＆Braak分期为0-II）的额叶新皮层的额叶相关新皮层中的γH2AX和DNA-PKcs的免疫组织化学和蛋白质印迹分析，以及衰老相关的β-半乳糖苷酶，并探讨了它们与认知障碍的关系 ud udResults udγH2AX+（rs = −0.36，P = 0.025）和DNA-PKcs +（rs = −0.39，P = 0.01）的人口代表样本中）神经元计数与较低的小精神状态检查得分相关。衰老相关的β-gal+锥体神经元水平的增加与DNA-PKcs +神经元的总数弱相关（P = 0.08），但与传统的衰老相关的信号分子（包括p53和p16）无关。 ud ud结论 udThe神经元DDR和认知障碍之间的相关性，独立于衰老的大脑中的AD病理学，可能暗示了神经元功能障碍的因果关系。

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