Astrocytes in Alzheimer’s disease (AD) exert a pivotal role in the maintenance of blood-brain barrier (BBB) integrity essentially through structural support and release of soluble factors. This study provides new insights into the vascular remodeling processes occurring in AD, and reveals, , a pathological profile of astrocytic secretion involving Vascular Endothelial Growth Factor (VEGF), Matrix Metalloproteinases (MMP)-9, MMP-2 and Endothelin-1 (ET-1). Cerebrospinal fluid (CSF) levels of VEGF, MMP-2/-9 were lower in patients belonging to the AD continuum, compared to aged-matched controls. CSF levels of VEGF and ET-1 positively correlated with MMP-9 but negatively with MMP-2, suggesting a complex vascular remodeling process occurring in AD. Only MMP-2 levels were significantly associated with CSF AD biomarkers. Conversely, higher MMP-2 (β = 0.411, p < 0.001), ET-1 levels (β = 0.344, p < 0.001) and VEGF (β = 0.221, p = 0.022), were associated with higher BBB permeability. Astrocytic-derived vascular remodeling factors are altered in AD, disclosing the failure of important protective mechanisms which proceed independently alongside AD pathology.

中文翻译：

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星形胶质细胞衍生的血管重塑因子与阿尔茨海默病的血脑屏障通透性独立相关


阿尔茨海默病 (AD) 中的星形胶质细胞主要通过结构支持和可溶性因子的释放，在维持血脑屏障 (BBB) 完整性方面发挥关键作用。这项研究为 AD 中发生的血管重塑过程提供了新的见解，并揭示了星形细胞分泌的病理特征，涉及血管内皮生长因子 (VEGF)、基质金属蛋白酶 (MMP)-9、MMP-2 和内皮素-1 (ET) -1）。与年龄匹配的对照组相比，AD 连续体患者的脑脊液 (CSF) VEGF、MMP-2/-9 水平较低。 CSF 的 VEGF 和 ET-1 水平与 MMP-9 呈正相关，但与 MMP-2 呈负相关，表明 AD 中发生了复杂的血管重塑过程。只有 MMP-2 水平与 CSF AD 生物标志物显着相关。相反，较高的 MMP-2（β = 0.411，p < 0.001）、ET-1 水平（β = 0.344，p < 0.001）和 VEGF（β = 0.221，p = 0.022）与较高的 BBB 通透性相关。星形细胞衍生的血管重塑因子在 AD 中发生改变，揭示了与 AD 病理学独立进行的重要保护机制的失败。