Ma Li-Yun, Song Jing-Hui, Gao Pei-Yang, Ou Ya-Nan, Fu Yan, Huang Liang-Yu, Wang Zuo-Teng, Zhang Dan-Dan, Cui Rui-Ping, Mi Yin-Chu, Tan Lan
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
J Neurochem. 2024 Sep;168(9):2532-2542. doi: 10.1111/jnc.16105. Epub 2024 Mar 27.
Though previous studies revealed the potential associations of elevated levels of plasma fibrinogen with dementia, there is still limited understanding regarding the influence of Alzheimer's disease (AD) biomarkers on these associations. We sought to investigate the interrelationships among fibrinogen, cerebrospinal fluid (CSF) AD biomarkers, and cognition in non-demented adults. We included 1996 non-demented adults from the Chinese Alzheimer's Biomarker and LifestylE (CABLE) study and 337 from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The associations of fibrinogen with AD biomarkers and cognition were explored using multiple linear regression models. The mediation analyses with 10 000 bootstrapped iterations were conducted to explore the mediating effects of AD biomarkers on cognition. In addition, interaction analyses and subgroup analyses were conducted to assess the influence of covariates on the relationships between fibrinogen and AD biomarkers. Participants exhibiting low Aβ42 were designated as A+, while those demonstrating high phosphorylated tau (P-tau) and total tau (Tau) were labeled as T+ and N+, respectively. Individuals with normal measures of Aβ42 and P-tau were categorized as the A-T- group, and those with abnormal levels of both Aβ42 and P-tau were grouped under A+T+. Fibrinogen was higher in the A+ subgroup compared to that in the A- subgroup (p = 0.026). Fibrinogen was higher in the A+T+ subgroup compared to that in the A-T- subgroup (p = 0.011). Higher fibrinogen was associated with worse cognition and Aβ pathology (all p < 0.05). Additionally, the associations between fibrinogen and cognition were partially mediated by Aβ pathology (mediation proportion range 8%-28%). Interaction analyses and subgroup analyses showed that age and ApoE ε4 affect the relationships between fibrinogen and Aβ pathology. Fibrinogen was associated with both cognition and Aβ pathology. Aβ pathology may be a critical mediator for impacts of fibrinogen on cognition.
尽管先前的研究揭示了血浆纤维蛋白原水平升高与痴呆症之间的潜在关联，但对于阿尔茨海默病（AD）生物标志物对这些关联的影响仍了解有限。我们试图研究非痴呆成年人中纤维蛋白原、脑脊液（CSF）AD生物标志物与认知之间的相互关系。我们纳入了来自中国阿尔茨海默病生物标志物与生活方式（CABLE）研究的1996名非痴呆成年人以及来自阿尔茨海默病神经影像倡议（ADNI）数据库的337名成年人。使用多元线性回归模型探讨纤维蛋白原与AD生物标志物及认知之间的关联。进行了10000次自抽样迭代的中介分析，以探讨AD生物标志物对认知的中介作用。此外，进行了交互分析和亚组分析，以评估协变量对纤维蛋白原与AD生物标志物之间关系的影响。Aβ42水平低的参与者被指定为A+，而磷酸化tau（P-tau）和总tau（Tau）水平高的参与者分别被标记为T+和N+。Aβ42和P-tau测量值正常的个体被归类为A-T-组，而Aβ42和P-tau水平均异常的个体被归为A+T+组。A+亚组中的纤维蛋白原高于A-亚组（p = 0.026）。A+T+亚组中的纤维蛋白原高于A-T-亚组（p = 0.011）。较高的纤维蛋白原与较差的认知和Aβ病理相关（所有p < 0.05）。此外，纤维蛋白原与认知之间的关联部分由Aβ病理介导（中介比例范围为8%-28%）。交互分析和亚组分析表明，年龄和载脂蛋白Eε4影响纤维蛋白原与Aβ病理之间的关系。纤维蛋白原与认知和Aβ病理均相关。Aβ病理可能是纤维蛋白原对认知影响的关键中介因素。
