Department of Otorhinolaryngology, Institute of Molecular Medicine and Max-Planck-Research, Ulm University, Ulm, Germany.
Neurology. 2012 Feb 21;78(8):569-77. doi: 10.1212/WNL.0b013e318247caa1. Epub 2012 Feb 8.
DNA damage accumulation in brain is associated with the development of Alzheimer disease (AD), but newly identified protein markers of DNA damage have not been evaluated in the diagnosis of AD and other forms of dementia.
Here, we analyzed the level of novel biomarkers of DNA damage and telomere dysfunction (chitinase activity, N-acetyl-glucosaminidase activity, stathmin, and EF-1α) in CSF of 94 patients with AD, 41 patients with non-AD dementia, and 40 control patients without dementia.
Enzymatic activity of chitinase (chitotriosidase activity) and stathmin protein level were significantly increased in CSF of patients with AD and non-AD dementia compared with that of no dementia control patients. As a single marker, chitinase activity was most powerful for distinguishing patients with AD from no dementia patients with an accuracy of 85.8% using a single threshold. Discrimination was even superior to clinically standard CSF markers that showed an accuracy of 78.4% (β-amyloid) and 77.6% (tau). Combined analysis of chitinase with other markers increased the accuracy to a maximum of 91%. The biomarkers of DNA damage were also increased in CSF of patients with non-AD dementia compared with no dementia patients, and the new biomarkers improved the diagnosis of non-AD dementia as well as the discrimination of AD from non-AD dementia.
Taken together, the findings in this study provide experimental evidence that DNA damage markers are significantly increased in AD and non-AD dementia. The biomarkers identified outperformed the standard CSF markers for diagnosing AD and non-AD dementia in the cohort investigated.
大脑中的 DNA 损伤积累与阿尔茨海默病（AD）的发展有关，但尚未评估新发现的 DNA 损伤蛋白标志物在 AD 和其他形式痴呆症的诊断中的作用。
在这里，我们分析了 94 例 AD 患者、41 例非 AD 痴呆患者和 40 例无痴呆对照组患者 CSF 中新型 DNA 损伤和端粒功能障碍生物标志物（几丁质酶活性、N-乙酰-氨基葡萄糖苷酶活性、stathmin 和 EF-1α）的水平。
与无痴呆对照组患者相比，AD 和非 AD 痴呆患者的 CSF 中几丁质酶（几丁质酶活性）和 stathmin 蛋白水平的酶活性显着增加。作为单一标志物，几丁质酶活性在区分 AD 患者和无痴呆患者方面最为有效，使用单一阈值的准确率为 85.8%。与临床标准 CSF 标志物相比，这种区分甚至更优越，后者的准确率分别为 78.4%（β-淀粉样蛋白）和 77.6%（tau）。几丁质酶与其他标志物的联合分析可将准确率提高到最高 91%。非 AD 痴呆患者的 CSF 中也增加了 DNA 损伤生物标志物，这些新的生物标志物改善了非 AD 痴呆症的诊断，并且可以区分 AD 和非 AD 痴呆症。
综上所述，本研究的结果提供了实验证据，表明 DNA 损伤标志物在 AD 和非 AD 痴呆症中显着增加。在研究的队列中，鉴定出的生物标志物在诊断 AD 和非 AD 痴呆症方面优于标准 CSF 标志物。
