Cerebral Cavernous Malformation (CCM)-like Vessel Lesion in the Aged ANKS1A -deficient Brain

In this study, we show that ANKS1A is specifically expressed in the brain endothelial cells of adult mice. 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 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 . Therefore, we hypothesize that ANKS1A may play a role in maintaining or stabilizing healthy blood vessels in the brain during aging.