■血浆胶质纤维酸性蛋白(GFAP),星形细胞生物标志物,以前曾与阿尔茨海默病(AD)状态有关,淀粉样蛋白水平,和老年人的记忆表现。星形胶质细胞增生/星形胶质细胞反应性可能影响认知结果的神经解剖学途径仍不清楚。我们评估了血浆GFAP和淀粉样蛋白水平是否对穹窿结构有协同作用,与AD相关的胆碱能通路密切相关。我们还研究了穹窿结构是否介导GFAP和言语记忆之间的关联。
■在一组无症状和有症状的老年人中(总n=99),我们评估了血浆GFAP,淀粉样蛋白-β42(Aβ42),其他AD相关蛋白,血管标记物,我们进行了全面的记忆测试。基于纤维束成像的方法用于评估具有全脑扩散指标的穹窿结构,以控制脑白质的弥漫性改变。
■在低血浆淀粉样β42(Aβ42)组的个体中,较高的血浆GFAP与较低的分数各向异性(FA;p=0.007)相关,较高的平均扩散系数(MD;p<0.001),较高的径向扩散系数(RD;p<0.001),和较高的轴向扩散率(DA;p=0.001)在左穹窿。这些关联独立于APOE基因状态,总tau和神经丝光的血浆水平,血浆血管生物标志物,和整个大脑扩散指标。在对低血浆Aβ42组(n=33)参与者的亚分析中,穹窿结构介导了较高的血浆GFAP水平与较低的言语记忆表现之间的关联。
■在淀粉样蛋白沉积较多的情况下,较高的血浆GFAP与穹窿微结构改变有关。我们还通过证明在低血浆Aβ42组中,左穹窿完整性可能是GFAP与言语记忆表现负相关的主要白质管道.总的来说,这些发现表明,星形胶质细胞增生/星形胶质细胞反应性可能在早期发挥作用,在AD发病机制中的关键作用,并进一步证明血浆中的高GFAP和低Aβ42可能反映了在不明记忆途径中特别有害的协同作用。
UNASSIGNED: Plasma glial fibrillary acidic protein (GFAP), an astrocytic biomarker, has previously been linked with Alzheimer\'s disease (AD) status, amyloid levels, and memory performance in older adults. The neuroanatomical pathways by which
astrogliosis/astrocyte reactivity might impact cognitive outcomes remains unclear. We evaluated whether plasma GFAP and amyloid levels had a synergistic effect on fornix structure, which is critically involved in AD-associated cholinergic pathways. We also examined whether fornix structure mediates associations between GFAP and verbal memory.
UNASSIGNED: In a cohort of both asymptomatic and symptomatic older adults (total n = 99), we assessed plasma GFAP, amyloid-β42 (Aβ42), other AD-related proteins, and vascular markers, and we conducted comprehensive memory testing. Tractography-based methods were used to assess fornix structure with whole brain diffusion metrics to control for diffuse alterations in brain white matter.
UNASSIGNED: In individuals in the low plasma amyloid-β42 (Aβ42) group, higher plasma GFAP was associated with lower fractional anisotropy (FA; p = 0.007), higher mean diffusivity (MD; p < 0.001), higher radial diffusivity (RD; p < 0.001), and higher axial diffusivity (DA; p = 0.001) in the left fornix. These associations were independent of APOE gene status, plasma levels of total tau and neurofilament light, plasma vascular biomarkers, and whole brain diffusion metrics. In a sub-analysis of participants in the low plasma Aβ42 group (n = 33), fornix structure mediated the association between higher plasma GFAP levels and lower verbal memory performance.
UNASSIGNED: Higher plasma GFAP was associated with altered fornix microstructure in the setting of greater amyloid deposition. We also expanded on our prior GFAP-verbal memory findings by demonstrating that in the low plasma Aβ42 group, left fornix integrity may be a primary white matter conduit for the negative associations between GFAP and verbal memory performance. Overall, these findings suggest that
astrogliosis/astrocyte reactivity may play an early, pivotal role in AD pathogenesis, and further demonstrate that high GFAP and low Aβ42 in plasma may reflect a particularly detrimental synergistic role in forniceal-memory pathways.