Abstract:
Inflammation is an important factor in Alzheimer\'s disease (AD). An NMR measurement in plasma, glycoprotein acetyls (GlycA), captures the overall level of protein production and glycosylation implicated in systemic inflammation. With its additional advantage of reducing biological variability, GlycA might be useful in monitoring the relationship between peripheral inflammation and brain changes relevant to AD. However, the associations between GlycA and these brain changes have not been fully evaluated. Here, we performed Spearman\'s correlation analyses to evaluate these associations cross-sectionally and determined whether GlycA can inform AD-relevant longitudinal measurements among participants in the Alzheimer\'s Disease Neuroimaging Initiative (n = 1506), with additional linear models and stratification analyses to evaluate the influences of sex or diagnosis status and confirm findings from Spearman\'s correlation analyses. We found that GlycA was elevated in AD patients compared to cognitively normal participants. GlycA correlated negatively with multiple concurrent regional brain volumes in females diagnosed with late mild cognitive impairment (LMCI) or AD. Baseline GlycA level was associated with executive function decline at 3-9 year follow-up in participants diagnosed with LMCI at baseline, with similar but not identical trends observed in the future decline of memory and entorhinal cortex volume. Results here indicated that GlycA is an inflammatory biomarker relevant to AD pathogenesis and that the stage of LMCI might be relevant to inflammation-related intervention.
摘要:
炎症是阿尔茨海默病(AD)的重要因素。等离子体中的核磁共振测量,糖蛋白乙酰基(GlycA),捕获全身炎症中涉及的蛋白质产生和糖基化的总体水平。凭借其减少生物变异性的额外优势,GlycA可能有助于监测外周炎症和与AD相关的大脑变化之间的关系。然而,GlycA与这些大脑变化之间的关联尚未得到充分评估.这里,我们进行了Spearman的相关性分析,以横截面方式评估这些关联,并确定GlycA是否可以在阿尔茨海默病神经影像学计划(n=1506)的参与者中告知AD相关的纵向测量,使用其他线性模型和分层分析来评估性别或诊断状态的影响,并确认Spearman\的相关分析结果。我们发现,与认知正常参与者相比,GlycA在AD患者中升高。GlycA与诊断为晚期轻度认知障碍(LMCI)或AD的女性的多个并发区域脑体积呈负相关。基线GlycA水平与基线诊断为LMCI的参与者在3-9年随访时执行功能下降相关。在未来的记忆力和内嗅皮层体积下降中观察到相似但不相同的趋势。这里的结果表明GlycA是与AD发病机制相关的炎症生物标志物,并且LMCI的阶段可能与炎症相关的干预相关。