Abstract：
The advent of proteomics offers an unprecedented opportunity to predict dementia onset. We examined this in data from 52,645 adults without dementia in the UK Biobank, with 1,417 incident cases and a follow-up time of 14.1 years. Of 1,463 plasma proteins, GFAP, NEFL, GDF15 and LTBP2 consistently associated most with incident all-cause dementia (ACD), Alzheimer\'s disease (AD) and vascular dementia (VaD), and ranked high in protein importance ordering. Combining GFAP (or GDF15) with demographics produced desirable predictions for ACD (area under the curve (AUC) = 0.891) and AD (AUC = 0.872) (or VaD (AUC = 0.912)). This was also true when predicting over 10-year ACD, AD and VaD. Individuals with higher GFAP levels were 2.32 times more likely to develop dementia. Notably, GFAP and LTBP2 were highly specific for dementia prediction. GFAP and NEFL began to change at least 10 years before dementia diagnosis. Our findings strongly highlight GFAP as an optimal biomarker for dementia prediction, even more than 10 years before the diagnosis, with implications for screening people at high risk for dementia and for early intervention.
摘要：
蛋白质组学的出现为预测痴呆症的发病提供了前所未有的机会。我们在英国生物库的52,645名没有痴呆症的成年人的数据中检查了这一点，1,417例事件，随访时间为14.1年。在1,463种血浆蛋白中，GFAP,NEFL,GDF15和LTBP2始终与全因痴呆症（ACD）相关，阿尔茨海默病（AD）和血管性痴呆（VaD），在蛋白质重要性排序中排名很高。将GFAP(或GDF15)与人口统计学组合产生对ACD(曲线下面积(AUC)=0.891)和AD(AUC=0.872)(或VaD(AUC=0.912))的期望预测。在预测超过10年的ACD时也是如此，AD和VaD。GFAP水平较高的人患痴呆症的可能性是其2.32倍。值得注意的是,GFAP和LTBP2对痴呆预测具有高度特异性。GFAP和NEFL在痴呆诊断前至少10年开始改变。我们的研究结果强烈强调GFAP是预测痴呆症的最佳生物标志物，甚至在诊断前10多年，对筛查痴呆症高危人群和早期干预有影响。
