Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Huddinge, Sweden.
Division of Clinical Geriatrics, Department of Neurobiology, Care Sciences and Society, Karolinska Institute, Huddinge, Sweden.
Neurobiol Aging. 2020 Apr;88:61-70. doi: 10.1016/j.neurobiolaging.2019.12.012. Epub 2019 Dec 20.
Progranulin plays an important role in neuroinflammation in Alzheimer's disease (AD) pathophysiology, being upregulated by activated microglia. This study assessed whether cerebrospinal fluid levels of progranulin correlated with structural neuroimaging measures and cognition in 122 cognitively normal individuals, 81 mild cognitive impairment, and 70 AD patients from the Alzheimer's Disease Neuroimaging Initiative. Cognitively normal subjects were classified into 3 groups using the AT(N) system, whereas all mild cognitive impairment and AD patients were A+/TN+. Correlations between progranulin with neuroanatomical measures and cognitive decline were performed within each group. Progranulin was associated with cortical thickening in parietal, occipital, and frontal regions in cognitively normal individuals with amyloid pathology. These subjects also showed cortical thickening compared with A-/TN- subjects, an effect that was partially mediated by progranulin. In addition, higher progranulin correlated with longitudinal cognitive decline. The association between progranulin and cortical thickening, together with regional "brain swelling" in A+/TN- subjects, suggests progranulin contributes to the neuroinflammatory structural changes in preclinical AD.
颗粒蛋白前体在阿尔茨海默病（AD）的神经炎症病理生理学中起着重要作用，其水平可被激活的小胶质细胞上调。本研究评估了来自阿尔茨海默病神经影像学倡议的 122 名认知正常个体、81 名轻度认知障碍和 70 名 AD 患者的脑脊液颗粒蛋白前体水平是否与结构神经影像学测量和认知功能相关。认知正常者使用 AT(N)系统分为 3 组，而所有轻度认知障碍和 AD 患者均为 A+/TN+。在每组内进行颗粒蛋白前体与神经解剖学测量和认知下降之间的相关性分析。在有淀粉样蛋白病理的认知正常个体中，颗粒蛋白前体与顶叶、枕叶和额叶区域的皮质增厚相关。与 A-/TN- 受试者相比，这些受试者也表现出皮质增厚，这种效应部分是由颗粒蛋白前体介导的。此外，较高的颗粒蛋白前体与纵向认知下降相关。颗粒蛋白前体与皮质增厚之间的关联，以及 A+/TN- 受试者的区域性“脑肿胀”，提示颗粒蛋白前体有助于 AD 临床前阶段的神经炎症性结构变化。
