Department of Neurology, Faculty of Medicine, Oita University, Oita 879-5593, Japan.
Kameda Medical Center, Chiba 296-8602, Japan.
Biomolecules. 2021 Oct 11;11(10):1496. doi: 10.3390/biom11101496.
This study aimed to explore whether cerebrospinal fluid (CSF) levels of matrix metalloproteinases (MMPs), and their inhibitors (TIMPs) were associated with brain amyloid deposition, cortical glucose metabolism, and white matter lesions (WMLs) in individuals with amnestic mild cognitive impairment (MCI). A total of 33 individuals with amnestic MCI (mean age, 75.6 years) underwent C-Pittsburgh compound B positron emission tomography (PiB-PET), F-fluorodeoxyglucose positron emission tomography, magnetic resonance imaging or computed tomography, and CSF analysis. PET uptake of the frontal and temporoparietal lobes and posterior cingulate gyrus was assessed using the cerebellar cortex as the reference region. WMLs were assessed by the Fazekas scale. CSF levels of MMPs and TIMPs were measured with bead-based multiplex assays. After adjusting for covariates, multiple linear regression analysis showed that CSF levels of MMP-2 were negatively correlated with global PiB uptake ( = 0.035), especially in the parietotemporal lobe and posterior cingulate gyrus ( = 0.016 and = 0.041, respectively). Moreover, CSF levels of MMP-7 were positively correlated with the severity of WMLs ( = 0.033). CSF levels of MMP-2 and MMP-7 are associated with brain amyloid deposition and severity of WMLs, respectively. These findings provide valuable insights into the role of MMPs in amyloid β catabolism and blood-brain barrier integration at the MCI stage.
本研究旨在探讨脑脊液(CSF)中基质金属蛋白酶(MMPs)及其抑制剂(TIMPs)水平是否与遗忘型轻度认知障碍(MCI)个体的脑内淀粉样蛋白沉积、皮质葡萄糖代谢和白质病变(WMLs)有关。共纳入 33 名遗忘型 MCI 患者(平均年龄 75.6 岁),行 C-Pittsburgh 复合 B 正电子发射断层扫描(PiB-PET)、F-氟脱氧葡萄糖正电子发射断层扫描、磁共振成像或计算机断层扫描和 CSF 分析。采用小脑皮质作为参照区评估额顶颞叶和后扣带回的 PET 摄取。采用 Fazekas 量表评估 WMLs。采用基于珠的多重分析测定 CSF 中 MMPs 和 TIMPs 的水平。在调整协变量后,多元线性回归分析显示 MMP-2 的 CSF 水平与全局 PiB 摄取呈负相关( = 0.035),尤其是在顶颞叶和后扣带回( = 0.016 和 = 0.041)。此外,MMP-7 的 CSF 水平与 WMLs 的严重程度呈正相关( = 0.033)。MMP-2 和 MMP-7 的 CSF 水平分别与脑内淀粉样蛋白沉积和 WMLs 的严重程度相关。这些发现为 MMPs 在淀粉样β代谢和血脑屏障整合方面在 MCI 阶段的作用提供了有价值的见解。