Neuroinflammation in Alzheimer's disease wanes with age

Neuroinflammation in Alzheimer's disease wanes with age
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DOI:
10.1186/1742-2094-8-171
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发表时间:
2011-12-07
影响因子:
9.3
通讯作者:
van Gool, Willem A.
van Gool, Willem A.
中科院分区:
医学1区
文献类型:
--
作者:
Hoozemans, Jeroen J. M.;Rozemuller, Annemieke J. M.;van Gool, Willem A.

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背景:炎症是阿尔茨海默病(AD)的一个显著特征。有人提出,衰老会影响大脑炎症的功能,从而导致AD等与年龄有关的疾病的发展。然而,炎症与AD临床表型之间的年龄依赖关系从未被研究过。方法:在本研究中,我们分析了临床和病理证实的AD和对照病例的神经炎症反应特征与年龄(52-97岁)的关系。应用CD68 (KP1)、HLA II类(CR3/43)和胶质原纤维酸性蛋白(GFAP)抗体,免疫组化方法评估19例对照和19例AD患者中颞叶皮层小胶质细胞和星形胶质细胞的发生情况。结果:通过测量免疫反应性的面积密度,我们发现80岁以下阿尔茨海默病患者的小胶质细胞和星形胶质细胞明显多于老年阿尔茨海默病患者。此外,KP1、CR3/43和GFAP的存在随着AD患者年龄的增加而显著降低。结论:我们的数据表明,相对年轻的患者与老年患者相比,神经炎症与AD之间的相关性更强。炎症和阿尔茨海默病临床表型之间的这种年龄依赖关系对生物标志物的解释和疾病的治疗具有重要意义。
Background: Inflammation is a prominent feature in Alzheimer's disease (AD). It has been proposed that aging has an effect on the function of inflammation in the brain, thereby contributing to the development of age-related diseases like AD. However, the age-dependent relationship between inflammation and clinical phenotype of AD has never been investigated.Methods: In this study we have analysed features of the neuroinflammatory response in clinically and pathologically confirmed AD and control cases in relation to age (range 52-97 years). The mid-temporal cortex of 19 controls and 19 AD cases was assessed for the occurrence of microglia and astrocytes by immunohistochemistry using antibodies directed against CD68 (KP1), HLA class II (CR3/43) and glial fibrillary acidic protein (GFAP).Results: By measuring the area density of immunoreactivity we found significantly more microglia and astrocytes in AD cases younger than 80 years compared to older AD patients. In addition, the presence of KP1, CR3/43 and GFAP decreases significantly with increasing age in AD.Conclusion: Our data suggest that the association between neuroinflammation and AD is stronger in relatively young patients than in the oldest patients. This age-dependent relationship between inflammation and clinical phenotype of AD has implications for the interpretation of biomarkers and treatment of the disease.