Shu Hao, Ding Gangyu, Xu Xiaona, Huang Xuerong, He Ruqian
Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical University (Ruian People's Hospital), Wenzhou, Zhejiang, China.
Department of Neurology, Jiading District Central Hospital Affiliated Shanghai University of Medicine and Health Sciences, Jiading, Shanghai, China.
Front Aging Neurosci. 2025 Jan 14;16:1481526. doi: 10.3389/fnagi.2024.1481526. eCollection 2024.
Recent studies have shown that cerebrospinal fluid (CSF) levels of soluble triggering receptor expressed on myeloid cells 1 (sTREM1) are elevated in individuals with Alzheimer's disease (AD), though the relationship between CSF sTREM1 and hippocampal atrophy remains to be elucidated. The primary aim of this study was to investigate the association between CSF sTREM1 levels and longitudinal changes in hippocampal volumes, and to determine if this relationship is moderated by cognitive status.
We included 576 participants, comprising 152 cognitively unimpaired (CU) and 424 cognitively impaired (CI) individuals. In the cross-sectional analyses, Pearson's correlation tests were conducted to examine the relationship between baseline CSF sTREM1 levels and hippocampal volumes in both CU and CI participants. For the longitudinal analyses, a linear mixed-effects model was employed to assess the significance of the three-way interaction between CSF sTREM1 levels, cognitive status, and follow-up time on adjusted hippocampal volume (aHV). Further stratified analyses based on cognitive status were performed to dissect the specific effects within each group.
Our findings revealed significantly elevated baseline CSF sTREM1 levels in CI participants compared to CU participants. Cross-sectional analyses demonstrated that CSF sTREM1 levels were negatively associated with hippocampal volumes in both CU and CI participants. In the longitudinal analyses, the three-way interaction between CSF sTREM1 levels, cognitive status, and follow-up time was found to be significant for aHV. Stratified analyses indicated that, in CI participants, higher CSF sTREM1 levels were associated with a more accelerated rate of hippocampal atrophy, whereas no such association was observed in CU participants.
These results underscore the complex interplay between neuroinflammation, as reflected by CSF sTREM1 levels, hippocampal atrophy, and cognitive decline. The data suggest that neuroinflammation may contribute differently to hippocampal atrophy rates in CI versus CU individuals, highlighting the potential for targeted anti-inflammatory interventions in the prevention and treatment of AD.
最近的研究表明，阿尔茨海默病（AD）患者的脑脊液（CSF）中髓样细胞表达的可溶性触发受体1（sTREM1）水平升高，尽管CSF sTREM1与海马萎缩之间的关系仍有待阐明。本研究的主要目的是调查CSF sTREM1水平与海马体积纵向变化之间的关联，并确定这种关系是否受认知状态的调节。
我们纳入了576名参与者，包括152名认知未受损（CU）和424名认知受损（CI）个体。在横断面分析中，进行Pearson相关检验以检查CU和CI参与者的基线CSF sTREM1水平与海马体积之间的关系。对于纵向分析，采用线性混合效应模型来评估CSF sTREM1水平、认知状态和随访时间对调整后海马体积（aHV）的三元交互作用的显著性。基于认知状态进行进一步的分层分析，以剖析每组中的具体影响。
我们的研究结果显示，与CU参与者相比，CI参与者的基线CSF sTREM1水平显著升高。横断面分析表明，CU和CI参与者的CSF sTREM1水平均与海马体积呈负相关。在纵向分析中，发现CSF sTREM1水平、认知状态和随访时间之间的三元交互作用对aHV具有显著性。分层分析表明，在CI参与者中，较高的CSF sTREM1水平与海马萎缩速度加快相关，而在CU参与者中未观察到这种关联。
这些结果强调了CSF sTREM1水平所反映的神经炎症、海马萎缩和认知衰退之间的复杂相互作用。数据表明，神经炎症对CI与CU个体海马萎缩率的影响可能不同，这突出了针对性抗炎干预在AD预防和治疗中的潜力。
