Brain senescence is associated with impaired endothelial barrier function, angiogenic and inflammatory activity, and propensity to brain hemorrhage. The same pathological changes occur in cerebral cavernous malformations (CCM), a genetic neurovascular anomaly. We hypothesized common transcriptomic and plasma cytokine signatures in the aging brain and CCM. We identified 320 genes [fold change ≥1.5; p < 0.05; false discovery rate (FDR) corrected] commonly dysregulated in the aging brain and CCM. Ontology and pathway analyses of the common differentially expressed genes were related to inflammation and extracellular matrix organization. Plasma levels of C-reactive protein and angiopoietin-2 were significantly greater in older compared to younger healthy non-CCM subjects and were also greater in CCM (Sporadic and Familial) subjects regardless of age (all: p < 0.05; FDR corrected). Plasma levels of vascular endothelial growth factor were significantly greater in older compared to younger subjects, in both healthy non-CCM and Sporadic-CCM groups (all: p_adj < 0.05). Plasma levels of vascular endothelial growth factor were also significantly greater in Familial-CCM cases with germ line mutations regardless of age (all: p_adj < 0.05) compared to both healthy non-CCM and Sporadic-CCM subjects. Brain white matter vascular permeability assessed by MRI followed the same pattern as vascular endothelial growth factor across all groups. In addition, quantitative susceptibility mapping of brain white matter, a measure of iron deposition, was increased in older compared to younger healthy non-CCM subjects. Genetic aberrations, plasma molecules, and imaging biomarkers in a well characterized Mendelian neurovascular disease may also be applicable in the aging brain.

脑衰老与受损的内皮屏障功能、血管生成和炎症活动以及脑出血倾向有关。同样的病理变化也发生在脑海绵状血管瘤 (CCM) 中，这是一种遗传性神经血管异常。我们假设老化大脑和 CCM 中常见的转录组和血浆细胞因子特征。我们鉴定了 320 个基因 [倍数变化≥1.5；p < 0.05; 错误发现率 (FDR) 更正] 通常在老化的大脑和 CCM 中失调。常见差异表达基因的本体和通路分析与炎症和细胞外基质组织有关。与年轻的健康非 CCM 受试者相比，老年人的血浆 C 反应蛋白和血管生成素 2 水平显着高于健康的非 CCM 受试者，并且无论年龄如何，CCM（散发性和家族性）受试者的血浆水平也更高（所有：p  < 0.05；FDR 校正）。与年轻受试者相比，健康的非 CCM 组和散发性 CCM 组的老年人血浆血管内皮生长因子水平显着升高（所有：p _adj < 0.05)。 与健康的非 CCM 和散发性 CCM 受试者相比，无论年龄大小（所有： p _adj < 0.05） ，具有生殖系突变的家族性 CCM 病例的血浆血管内皮生长因子水平也显着升高。通过 MRI 评估的脑白质血管通透性在所有组中都遵循与血管内皮生长因子相同的模式。此外，与年轻的健康非 CCM 受试者相比，老年人的脑白质定量易感性图（一种铁沉积量度）有所增加。良好表征的孟德尔神经血管疾病中的遗传畸变、血浆分子和成像生物标志物也可能适用于衰老的大脑。