Department of Pathology, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
J Neuroinflammation. 2011 Dec 7;8:171. doi: 10.1186/1742-2094-8-171.
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.
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).
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.
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.
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 等与年龄相关的疾病的发展。然而,炎症与 AD 的临床表型之间的年龄相关性从未被研究过。
在这项研究中,我们分析了与年龄(52-97 岁)相关的临床和病理确诊的 AD 和对照组病例中神经炎症反应的特征。使用针对 CD68(KP1)、HLA Ⅱ类(CR3/43)和神经胶质纤维酸性蛋白(GFAP)的抗体,通过免疫组织化学方法评估 19 例对照和 19 例 AD 病例的中颞皮质中微胶质细胞和星形胶质细胞的发生情况。
通过测量免疫反应的面积密度,我们发现,与年龄较大的 AD 患者相比,年龄小于 80 岁的 AD 患者的微胶质细胞和星形胶质细胞明显更多。此外,在 AD 患者中,KP1、CR3/43 和 GFAP 的存在随着年龄的增加而显著减少。
我们的数据表明,神经炎症与 AD 之间的关联在相对年轻的患者中比在最年长的患者中更强。AD 炎症与临床表型之间的这种年龄相关性对生物标志物的解释和疾病的治疗具有重要意义。