Cao Yumeng, Salvati Lindsay R, Chen Jiachen, Ragab Ahmed, Mez Jesse, Satizabal Claudia L, Alosco Michael L, Fang Yuan, Qiu Wei Qiao, Lunetta Kathryn L, Murabito Joanne M, Doyle Margaret F
Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
Boston University Alzheimer's Disease Research Center, BU CTE Center, Department of Neurology, Boston University Chobanian and Avedisian School of Medicine, Boston, Massachusetts, USA.
J Gerontol A Biol Sci Med Sci. 2025 May 5;80(6). doi: 10.1093/gerona/glaf067.
Emerging evidence supports the central role of the immune system in brain health, yet little is known about the role of circulating immune cells and cognitive function or brain health in dementia-free populations. We investigated the association of 43 immune cells with cognitive function, structural brain imaging, and incident dementia in Framingham Heart Study Offspring participants. Immune cells were phenotyped by flow cytometry. Linear mixed effects models were used for cross-sectional associations between immune cells and 4 cognitive domain scores and 13 brain magnetic resonance imaging measurements. Cox proportional hazards regression models tested the relationship between immune cells and time to dementia. Models were adjusted for age, sex, education, cytomegalovirus status, and APOE genotype, with further adjustment for cardiovascular risk factors. Data was further stratified by cytomegalovirus status. Among 795 participants with cellular phenotyping, cognitive testing and brain imaging data (mean age 61, 52% women), there were no associations between immune cells and cognitive test scores. Several significant associations between immune cells and regional brain magnetic resonance imaging measurements were observed. Higher CD8+ cells [CD8+CD45RO-CCR7-CD27- (Teff), CD8+CD45RA+CD28-CD57+(TEMRA), CD8+CD27-CD28-] associated with greater cerebrum gray and frontal gray matter volumes and inclusion of cardiovascular risk factors strengthened the association. Among CMV+ participants, CD8+TEMRA and CD8+Teff cells were significantly associated with higher total gray and frontal gray matter volumes. No significant associations were observed between immune cells and incident all-cause or Alzheimer's disease dementia. The pathobiology underpinning the associations between immune cells and brain volumes require further study and validation in diverse samples.
新出现的证据支持免疫系统在大脑健康中的核心作用，但对于无痴呆人群中循环免疫细胞的作用以及认知功能或大脑健康的了解却很少。我们在弗雷明汉心脏研究后代参与者中调查了43种免疫细胞与认知功能、脑结构成像和新发痴呆之间的关联。通过流式细胞术对免疫细胞进行表型分析。线性混合效应模型用于免疫细胞与4个认知领域评分和13项脑磁共振成像测量之间的横断面关联。Cox比例风险回归模型测试了免疫细胞与痴呆发生时间之间的关系。模型对年龄、性别、教育程度、巨细胞病毒状态和APOE基因型进行了调整，并进一步对心血管危险因素进行了调整。数据按巨细胞病毒状态进一步分层。在795名有细胞表型分析、认知测试和脑成像数据的参与者中（平均年龄61岁，52%为女性），免疫细胞与认知测试评分之间没有关联。观察到免疫细胞与区域脑磁共振成像测量之间存在若干显著关联。较高的CD8+细胞[CD8+CD45RO-CCR7-CD27-（效应性T细胞）、CD8+CD45RA+CD2８-CD57+（终末分化记忆性T细胞）、CD8+CD27-CD28-]与更大的大脑灰质和额叶灰质体积相关，纳入心血管危险因素后这种关联得到加强。在巨细胞病毒阳性参与者中，CD8+终末分化记忆性T细胞和CD8+效应性T细胞与更高的总灰质和额叶灰质体积显著相关。未观察到免疫细胞与全因性或阿尔茨海默病痴呆的发生之间存在显著关联。免疫细胞与脑容量之间关联的病理生物学需要在不同样本中进一步研究和验证。
