Bernocchi Francesca, Bonomi Chiara Giuseppina, Assogna Martina, Moreschini Alessandra, Mercuri Nicola Biagio, Koch Giacomo, Martorana Alessandro, Motta Caterina
UOSD Centro Demenze, Policlinico Tor Vergata, University of Rome "Tor Vergata", viale Oxford 81, Rome 00133, Italy.
Non Invasive Brain Stimulation Unit, IRCCS Santa Lucia, via Ardeatina 306/354, Rome 00179, Italy.
Neurobiol Aging. 2024 Sep;141:66-73. doi: 10.1016/j.neurobiolaging.2024.05.002. Epub 2024 May 14.
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, in vivo, 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.
阿尔茨海默病（AD）中的星形胶质细胞在维持血脑屏障（BBB）完整性方面起着关键作用，主要通过结构支持和可溶性因子的释放来实现。这项研究为AD中发生的血管重塑过程提供了新的见解，并在体内揭示了星形胶质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，处于AD连续体中的患者脑脊液（CSF）中VEGF、MMP-2/-9的水平较低。CSF中VEGF和ET-1的水平与MMP-9呈正相关，但与MMP-2呈负相关，这表明AD中发生了复杂的血管重塑过程。只有MMP-2水平与CSF AD生物标志物显著相关。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。AD中星形胶质细胞衍生的血管重塑因子发生改变，揭示了重要保护机制的失效，这些机制在AD病理过程中独立进行。
