Neuropathology Unit, Department of Neurosciences, Centro Hospitalar do Porto, Porto, Portugal.
Life and Health Sciences Research Institute, University of Minho, Braga, Portugal.
Neuropathol Appl Neurobiol. 2018 Apr;44(3):298-313. doi: 10.1111/nan.12445. Epub 2017 Nov 27.
The association between the pathological features of AD and dementia is stronger in younger old persons than in older old persons suggesting that additional factors are involved in the clinical expression of dementia in the oldest old. Cumulative data suggests that neuroinflammation plays a prominent role in Alzheimer's disease (AD) and different studies reported an age-associated dysregulation of the neuroimmune system. Consequently, we sought to characterize the pattern of microglial cell activation and astrogliosis in brain post mortem tissue of pathologically confirmed cases of early and late onset AD (EOAD and LOAD) and determine their relation to age.
Immunohistochemistry (CD68 and glial fibrillary acidic protein) with morphometric analysis of astroglial profiles in 36 cases of AD and 28 similarly aged controls.
Both EOAD and LOAD groups had higher microglial scores in CA1, entorhinal and temporal cortices, and higher astroglial response in CA1, dentate gyrus, entorhinal and temporal cortices, compared to aged matched controls. Additionally, EOAD had higher microglial scores in subiculum, entorhinal and temporal subcortical white matter, and LOAD higher astrogliosis in CA2 region.
Overall, we found that the neuroinflammatory pathological markers in late stage AD human tissue to have a similar pattern in both EOAD and LOAD, though the severity of the pathological markers in the younger group was higher. Understanding the age effect in AD will be important when testing modifying agents that act on the neuroinflammation.
AD 的病理特征与痴呆的关联在较年轻的老年人中比在较年长的老年人中更强,这表明在最年长的老年人中,痴呆的临床表现涉及其他因素。累积数据表明,神经炎症在阿尔茨海默病(AD)中起重要作用,不同的研究报告了神经免疫系统与年龄相关的失调。因此,我们试图描述在病理证实的早发性和晚发性 AD(EOAD 和 LOAD)患者的大脑死后组织中,小胶质细胞激活和星形胶质细胞增生的模式,并确定其与年龄的关系。
对 36 例 AD 病例和 28 例年龄匹配的对照者的脑组织进行免疫组织化学(CD68 和胶质纤维酸性蛋白)染色,并进行星形胶质细胞形态计量分析。
与年龄匹配的对照组相比,EOAD 和 LOAD 组在 CA1、内嗅皮质和颞叶皮质的小胶质细胞评分更高,在 CA1、齿状回、内嗅皮质和颞叶皮质的星形胶质细胞反应更高。此外,EOAD 在海马旁回、内嗅皮质和颞叶皮质下白质中的小胶质细胞评分更高,LOAD 在 CA2 区的星形胶质细胞增生更高。
总的来说,我们发现晚期 AD 人类组织中的神经炎症病理标志物在 EOAD 和 LOAD 中具有相似的模式,尽管年轻组的病理标志物严重程度更高。在测试作用于神经炎症的修饰剂时,了解 AD 中的年龄效应将很重要。