TNFRSF1B Gene Variants and Related Soluble TNFR2 Levels Impact Resilience in Alzheimer's Disease.
TNFRSF1B Gene Variants and Related Soluble TNFR2 Levels Impact Resilience in Alzheimer's Disease.
复制标题
TNFRSF1B基因变异和相关可溶性TNFR2水平影响阿尔茨海默病的恢复力
DOI：
10.3389/fnagi.2021.638922
复制
发表时间：
2021
影响因子：
4.8
通讯作者：
Bekris LM
中科院分区：
文献类型：
--
作者：
Pillai JA;Bebek G;Khrestian M;Bena J;Bergmann CC;Bush WS;Leverenz JB;Bekris LM
肿瘤坏死因子受体2（TNFR2）促进下游神经元存活。这项纵向研究评估了编码TNFR2的TNFRSF1B基因及其可溶性形式（sTNFR2）的水平是否影响阿尔茨海默病（AD）生物标志物和临床结局。分析的数据包括阿尔茨海默病神经影像学倡议（ADNI）中的188例轻度认知障碍（MCI）和AD痴呆患者。此外，在48名在记忆诊所接受治疗的AD生物标志物阳性的MCI患者中进行了复制研究。评估了脑脊液（CSF）sTNFR2水平以及两个相关的TNFRSF1B基因单核苷酸多态性（SNP）rs976881和rs1061622。使用一般线性模型评价CSF sTNFR2水平和每种SNP与CSF t-tau和p-tau、认知域、MRI脑测量和对协变量（如APOE ε 4状态）进行调整后的纵向认知变化的关系的影响。在ADNI队列中，rs976881和CSF sTNFR2之间的显著相互作用调节CSF t-tau和p-tau水平;海马和全脑体积;以及数字跨度向前子测试分数。在复制队列中，rs976881和CSF sTNFR2之间的显著相互作用调节CSF p-tau。rs976881和CSF sTNFR2之间的显著相互作用也影响ADNI队列中12个月内的临床痴呆评定总分。TNFRSF1B变体rs976881和CSF sTNFR2水平之间的相互作用可调节多种AD相关严重程度标志物和认知领域。这种相互作用影响AD中的毒性相关临床结果，并支持sTNFR2作为有希望的治疗靶向候选物，以改善感兴趣的临床结果。
Tumor necrosis factor receptor 2 (TNFR2) promotes neuronal survival downstream. This longitudinal study evaluated whether the TNFRSF1B gene encoding TNFR2 and levels of its soluble form (sTNFR2) affect Alzheimer disease (AD) biomarkers and clinical outcomes. Data analyzed included 188 patients in the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had mild cognitive impairment (MCI) and AD dementia. Further, a replication study was performed in 48 patients with MCI with positive AD biomarkers who were treated at a memory clinic. Cerebrospinal fluid (CSF) sTNFR2 levels along with two related TNFRSF1B gene single nucleotide polymorphisms (SNPs) rs976881 and rs1061622 were assessed. General linear models were used to evaluate the effect of CSF sTNFR2 levels and each SNP in relationship to CSF t-tau and p-tau, cognitive domains, MRI brain measures, and longitudinal cognitive changes after adjustments were made for covariates such as APOE ε4 status. In the ADNI cohort, a significant interaction between rs976881 and CSF sTNFR2 modulates CSF t-tau and p-tau levels; hippocampal and whole brain volumes; and Digit Span Forwards subtest scores. In the replication cohort, a significant interaction between rs976881 and CSF sTNFR2 modulates CSF p-tau. A significant interaction between rs976881 and CSF sTNFR2 also impacts Clinical Dementia Rating Sum of Boxes scores over 12 months in the ADNI cohort. The interaction between TNFRSF1B variant rs976881 and CSF sTNFR2 levels was noted to modulate multiple AD-associated severity markers and cognitive domains. This interaction impacts resilience-related clinical outcomes in AD and lends support to sTNFR2 as a promising candidate for therapeutic targeting to improve clinical outcomes of interest.
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影响因子：
2.7
作者：
Medrano, L. M.;Taxonera, C.;Nunez, C.
通讯作者：
Nunez, C.
DOI：
10.1073/pnas.1605195113
发表时间：
2016-10-25
影响因子：
11.1
作者：
Dong, Yun;Fischer, Roman;Eisel, Ulrich L. M.
通讯作者：
Eisel, Ulrich L. M.
影响因子：
--
作者：
Biffi, Alessandro;Anderson, Christopher D.;Desikan, Rahul S.;Sabuncu, Mert;Cortellini, Lynelle;Schmansky, Nick;Salat, David;Rosand, Jonathan
通讯作者：
Rosand, Jonathan
影响因子：
56.9
作者：
Beattie, EC;Stellwagen, D;Malenka, RC
通讯作者：
Malenka, RC
影响因子：
4.9
作者：
Glossop JR;Dawes PT;Nixon NB;Mattey DL
通讯作者：
Mattey DL