背景:血脑屏障(BBB)改变可能通过各种机制导致AD病理,包括受损的淀粉样蛋白-β(Aβ)清除和神经炎症。可溶性血小板衍生生长因子受体β(sPDGFRβ)已成为BBB完整性的潜在生物标志物。动态对比增强磁共振成像(DCE-MRI)可直接评估BBB渗透性。然而,血脑屏障功能障碍之间的关系,认知障碍,AD病理仍不清楚,与文献中不一致的发现。
方法:我们使用来自DELCODE和DESCRIBE队列的数据进行了一项横断面研究,以调查认知正常(NC)参与者的BBB功能障碍,轻度认知障碍(MCI),和AD痴呆症。使用DCE-MRI评估BBB功能,并测量脑脊液中的sPDGFRβ水平,并测量AD生物标志物Aβ和tau。在一部分患者中,分析了CSF/血浆白蛋白比值(QAlb)作为BBB完整性的标准标志物和神经炎症标志物.
结果:91名参与者(NC:44,MCI:21,AD:26)被纳入分析。平均年龄74.4岁,42%是女性。在AD组(Ktrans:0.55×10-3min-1±0.74×10-3min-1),但在MCI组(Ktrans:0.177×10-3min-1±0.22×10-3min-1)中观察到海马BBB破坏增加,与NC组相比(Ktrans:0.19×10-3min-1±0.37×10-3min-1,p<0.01)。sPDGFRβ在认知组之间没有显着差异。然而,sPDGFRβ水平与年龄显著相关(r=0.33,p<0.01),独立于血管危险因素。Further,sPDGFRβ与可溶性Aβ水平(Aβ40:r=.57,p<.01;Aβ42:r=.39,p<.01)和YKL-40(r=.53,p<.01)呈显著正相关,神经炎症的标志.sPDGFRβ/DCE-MRI与总体AD生物标志物阳性或APOE状态无关。
结论:在痴呆症中,但没有MCI,观察到海马BBB破坏。sPDGFRβ随着年龄的增长而增加,并且与神经炎症相关,与认知障碍无关。Aβ和sPDGFRβ之间的关联可能表明双向关系,反映了可溶性Aβ的周细胞清除和/或Aβ的血管毒性。
BACKGROUND: Blood-brain barrier (BBB) alterations may contribute to AD pathology through various mechanisms, including impaired amyloid-β (Aβ) clearance and neuroinflammation. Soluble platelet-derived growth factor receptor beta (sPDGFRβ) has emerged as a potential biomarker for BBB integrity. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) offers a direct assessment of BBB permeability. However, the relationship between BBB dysfunction, cognitive impairment, and AD pathology remains unclear, with inconsistent findings in the literature.
METHODS: We conducted a cross-sectional study using data from the DELCODE and DESCRIBE cohorts to investigate BBB dysfunction in participants with normal cognition (NC), mild cognitive impairment (MCI), and AD dementia. BBB function was assessed using DCE-MRI and sPDGFRβ levels in cerebrospinal fluid and AD biomarkers Aβ and tau were measured. In a subset of patients, the CSF/plasma-ratio of albumin (QAlb) as a standard marker of BBB integrity and markers of neuroinflammation were analyzed.
RESULTS: 91 participants (NC: 44, MCI: 21, AD: 26) were included in the analysis. The average age was 74.4 years, 42% were female. Increased hippocampal BBB disruption was observed in the AD-group (Ktrans: 0.55 × 10- 3 min- 1 ± 0.74 × 10- 3 min- 1) but not the MCI-group (Ktrans: 0.177 × 10- 3 min- 1 ± 0.22 × 10- 3 min- 1), compared to the NC group (Ktrans: 0.19 × 10- 3 min- 1 ± 0.37 × 10- 3 min- 1, p < .01). sPDGFRβ was not significantly different between the cognitive groups. However, sPDGFRβ levels were significantly associated with age (r = .33, p < .01), independent of vascular risk factors. Further, sPDGFRβ showed significant positive associations with soluble Aβ levels (Aβ40: r = .57, p < .01; Aβ42: r = .39, p < .01) and YKL-40 (r = .53, p < .01), a marker of neuroinflammation. sPDGFRβ/DCE-MRI was not associated with overall AD biomarker positivity or APOE-status.
CONCLUSIONS: In dementia, but not MCI, hippocampal BBB disruption was observed. sPDGFRβ increased with age and was associated with neuroinflammation independent of cognitive impairment. The association between Aβ and sPDGFRβ may indicate a bidirectional relationship reflecting pericytes\' clearance of soluble Aβ and/or vasculotoxic properties of Aβ.