In this study, we show that ANKS1A is specifically expressed in the brain endothelial cells of adult mice. ANKS1A deficiency in adult mice does not affect the differentiation, growth, or patterning of the cerebrovascular system; however, its absence significantly impacts the cerebrovascular system of the aged brain. In aged ANKS1A knock-out (KO) brains, vessel lesions exhibiting cerebral cavernous malformations (CCMs) are observed. In addition, CCM-like lesions show localized peripheral blood leakage into the brain. The CCM-like lesions reveal immune cells infiltrating the parenchyma. The CCM-like lesions also contain significantly fewer astrocyte endfeets and tight junctions, indicating that the integrity of the BBB has been partially compromised. CCM-like lesions display increased fibronectin expression in blood vessels, which is also confirmed in cultured endothelial cells deficient for ANKS1A. Therefore, we hypothesize that ANKS1A may play a role in maintaining or stabilizing healthy blood vessels in the brain during aging.

中文翻译：

---

ANKS1A 缺陷的老年大脑中的脑海绵状血管畸形 (CCM) 样血管病变。

在这项研究中，我们发现 ANKS1A 在成年小鼠的脑内皮细胞中特异性表达。成年小鼠的ANKS1A缺陷不会影响脑血管系统的分化、生长或模式；然而，它的缺乏会显着影响老年大脑的脑血管系统。在老化的ANKS1A敲除 (KO) 大脑中，观察到表现出脑海绵状血管瘤 (CCM) 的血管病变。此外，CCM 样病变显示局部外周血渗漏到大脑中。CCM 样病变显示免疫细胞浸润实质。CCM 样病变还包含明显较少的星形胶质细胞末端和紧密连接，表明 BBB 的完整性已部分受损。CCM 样病变显示血管中纤连蛋白表达增加，这在培养的ANKS1A缺陷的内皮细胞中也得到证实。因此，我们假设 ANKS1A 可能在衰老过程中维持或稳定大脑血管健康方面发挥作用。