Shoushtari Sara I, Liaw Easton, Alluri Sreevardhan, Sheikh Zahra, Kumar Sudhir, Huynh Courtney, Schmidt Insa M, Ness Steven, Chen Xuejing, Siegel Nicole H, Waikar Sushrut S, Stein Thor D, Lu Weining, Subramanian Manju L
Boston University Chobanian & Avedisian School of Medicine, Boston, MA 02118.
Boston University Sargent College of Health and Rehabilitation Sciences, Boston, MA 02215.
bioRxiv. 2025 Jul 2:2025.05.03.652072. doi: 10.1101/2025.05.03.652072.
Slit Guidance Ligand 2 (SLIT2) binds Roundabout (ROBO) guidance receptors to direct axon pathfinding and neuron migration during nervous system development. SLIT2 expression has previously been linked to dementia risk.
To study the association between SLIT2 expression in human vitreous humor and plasma samples and neurocognitive test scores in a cross-sectional cohort study utilizing a novel, highly-sensitive Meso Scale Discovery (MSD) assay for SLIT2 detection.
Seventy-nine individuals with a mean age of 55.79 ± 12.03 years underwent eye surgery with collection of vitreous humor, blood (plasma) collection, and neurocognitive assessment. Vitreous humor and plasma samples were analyzed by SLIT2 MSD electrochemiluminescence immunoassay. Associations between SLIT2 levels in vitreous humor and plasma were analyzed using GraphPad Prism.
We found up to a 7-fold higher level of SLIT2 in human vitreous humor compared to plasma. Lower vitreous SLIT2 levels were associated with a lower Montreal Cognitive Assessment (MoCA) score and Immediate Recall Verbatim (IRV) z-score, and higher plasma SLIT2 was associated with a lower MoCA score. In multivariate analysis using single and multiple predictor models, the same significant associations were found when adjusted for age, sex, race, diabetic status, diabetic retinopathy status, glaucoma status, and Apolipoprotein E (APOE) genotype.
SLIT2 protein levels are significantly associated with MoCA score and IRV z-score in middle-aged individuals. The relationship remained significant when adjusted for demographics, co-morbidity, and APOE genotype, suggesting SLIT2 may be a sensitive biomarker for detection of mild cognitive impairment and early dementia, and warrants further studies.
Slit引导配体2（SLIT2）与Roundabout（ROBO）引导受体结合，在神经系统发育过程中指导轴突寻路和神经元迁移。SLIT2表达先前已与痴呆风险相关联。
在一项横断面队列研究中，利用一种新型、高灵敏度的Meso Scale Discovery（MSD）检测法检测SLIT2，研究人玻璃体液和血浆样本中SLIT2表达与神经认知测试分数之间的关联。
79名平均年龄为55.79±12.03岁的个体接受了眼科手术，同时采集了玻璃体液、血液（血浆）并进行了神经认知评估。通过SLIT2 MSD电化学发光免疫分析法分析玻璃体液和血浆样本。使用GraphPad Prism分析玻璃体液和血浆中SLIT2水平之间的关联。
我们发现人玻璃体液中SLIT2水平比血浆中高7倍。玻璃体液中较低的SLIT2水平与较低的蒙特利尔认知评估（MoCA）分数和即刻逐字回忆（IRV）z分数相关，而较高的血浆SLIT2水平与较低的MoCA分数相关。在使用单预测模型和多预测模型的多变量分析中，在对年龄、性别、种族、糖尿病状态、糖尿病视网膜病变状态、青光眼状态和载脂蛋白E（APOE）基因型进行调整后，发现了相同的显著关联。
SLIT2蛋白水平与中年个体的MoCA分数和IRV z分数显著相关。在对人口统计学、合并症和APOE基因型进行调整后，这种关系仍然显著，表明SLIT2可能是检测轻度认知障碍和早期痴呆的敏感生物标志物，值得进一步研究。
