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.

中文翻译：

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脑脊液颗粒蛋白前体与阿尔茨海默病早期皮质厚度增加有关

颗粒蛋白前体在阿尔茨海默病 (AD) 病理生理学的神经炎症中起重要作用，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计划的 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相关。使用 AT(N) 系统将认知正常的受试者分为 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能力下降之间的相关性。颗粒蛋白前体与具有淀粉样蛋白病理的认知正常个体的顶叶、枕叶和额叶区域的皮质增厚有关。与 A-/TN- 受试者相比，这些受试者还表现出皮质增厚，这种作用部分由颗粒蛋白前体介导。此外，较高的颗粒蛋白前体与纵向认知能力下降相关。颗粒蛋白前体和皮质增厚之间的关联，以及 A+/TN- 受试者的局部“脑肿胀”，表明颗粒蛋白前体有助于临床前 AD 中的神经炎症结构变化。