Royall Donald R, Al-Rubaye Safa, Bishnoi Ram, Palmer Raymond F
Department of Psychiatry, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
Department of Medicine, the University of Texas Health Science Center, San Antonio, Texas, United States of America.
PLoS One. 2017 Mar 14;12(3):e0172268. doi: 10.1371/journal.pone.0172268. eCollection 2017.
The latent variable "δ" (for "dementia") appears to be uniquely responsible for the dementing aspects of cognitive impairment. Age, depression, gender and the apolipoprotein E (APOE) e4 allele are independently associated with δ. In this analysis, we explore serum proteins as potential mediators of APOE's specific association with δ in a large, ethnically diverse longitudinal cohort, the Texas Alzheimer's Research and Care Consortium (TARCC). APOE was associated only with C-Reactive Protein (CRP), Adiponectin (APN) and Amphiregulin (AREG), although the latter two's associations did not survive Bonferroni correction for multiple comparisons. All three proteins were associated with δ and had weak potential mediation effects on APOE's association with that construct. Our findings suggest that APOE's association with cognitive performance is specific to δ and partially mediated by serum inflammatory proteins. The majority of APOE's significant unadjusted effect on δ is unexplained. It may instead arise from direct central nervous system effects, possibly on native intelligence. If so, then APOE may exert a life-long influence over δ and therefore all-cause dementia risk.
潜在变量“δ”（代表“痴呆症”）似乎是认知障碍中导致痴呆症方面的唯一因素。年龄、抑郁、性别和载脂蛋白E（APOE）e4等位基因均与δ独立相关。在本分析中，我们在一个大型、种族多样的纵向队列——德克萨斯阿尔茨海默病研究与护理联盟（TARCC）中，探究血清蛋白作为APOE与δ特异性关联的潜在中介因素。APOE仅与C反应蛋白（CRP）、脂联素（APN）和双调蛋白（AREG）相关，尽管后两者的关联在多重比较的Bonferroni校正后未通过检验。这三种蛋白均与δ相关，且对APOE与该结构的关联具有微弱的潜在中介作用。我们的研究结果表明，APOE与认知表现的关联特定于δ，且部分由血清炎症蛋白介导。APOE对δ的大部分显著未调整效应无法解释。它可能反而源于对中枢神经系统的直接影响，可能作用于先天智力。如果是这样，那么APOE可能对δ产生终身影响，进而影响全因痴呆风险。
