Abstract：
The plasma proteome can mediate poor oral health problems (POHP)\'s link to incident dementia. We screened 37,269 UK Biobank participants 50-74 years old (2006-2010) for prevalent POHP, further tested against 1463 plasma proteins and incident dementia over up to 15 years of follow-up. Total effect (TE) of POHP-dementia through plasma proteomic markers was decomposed into pure indirect effect (PIE), interaction referent (INTREF), controlled direct effect (CDE), or mediated interaction (INTMED). POHP increased the risk of all-cause dementia by 17% (P < 0.05). Growth differentiation factor 15 (GDF15) exhibited the strongest mediating effects (PIE > 0, P < 0.001), explaining 28% the total effect of POHP on dementia, as a pure indirect effect. A first principal component encompassing top 4 mediators (GDF15, IL19, MMP12, and ACVRL1), explained 11% of the POHP-dementia effect as a pure indirect effect. Pathway analysis including all mediators (k = 173 plasma proteins) revealed the involvement of the immune system, signal transduction, metabolism, disease, and gene expression, while STRING analysis indicated that top mediators within the first principal component were also represented in the two largest proteomic clusters. The dominant biological GO pathway for the GDF15 cluster was GO:0007169 labeled as \"transmembrane receptor protein tyrosine kinase signaling pathway.\" Dementia is linked to POHP mediated by GDF15 among several proteomic markers.
摘要：
血浆蛋白质组可以介导不良的口腔健康问题（POHP）与痴呆的联系。我们筛选了37,269名50-74岁(2006-2010)的英国生物银行参与者流行的POHP，在长达15年的随访中，进一步测试了1463种血浆蛋白和偶发性痴呆。POHP-痴呆通过血浆蛋白质组标记的总效应(TE)被分解成纯间接效应(PIE),交互引用(INTREF)，受控直接效应(CDE)，或介导相互作用(INTMED)。POHP使全因痴呆的风险增加17%(P<0.05)。生长分化因子15(GDF15)的介导作用最强(PIE>0,P<0.001),解释了28%的POHP对痴呆症的总影响，作为纯粹的间接影响。第一个主要成分包括前4个介体(GDF15、IL19、MMP12和ACVRL1)，将11%的POHP-痴呆效应解释为纯粹的间接效应。包括所有介质（k=173血浆蛋白）的通路分析揭示了免疫系统的参与，信号转导，新陈代谢，疾病,和基因表达，而STRING分析表明，第一个主成分中的顶级介质也代表在两个最大的蛋白质组中。GDF15簇的主要生物GO途径是GO：0007169标记为跨膜受体蛋白酪氨酸激酶信号通路。“痴呆症与几种蛋白质组标记中GDF15介导的POHP有关。
