Abstract Number: Esoc2026a1902 the Role of Pericyte Ablation on Hypertension-Induced Cerebral Small Vessel Pathology and Cognition

Abstract Background and aims Aging is associated with cerebral small vessel disease that contribute significantly to cognitive impairment. Hypertension is a major risk factor for small vessel disease. Perivascular fibrosis disrupts cerebral waste clearance, and recent evidence suggests that pericytes may play a critical role in this process. Hence we aimed to investigate the role of pericytes in cognitive function, and cerebral waste clearance in a hypertension model using a transgenic mouse model with conditional pericyte ablation. Methods Conditional pericyte ablation was achieved by crossing CreER+/- mice with Rosa26-DTA176+/+ mice. Hypertension was induced in all animals using continuous subcutaneous infusion of angiotensin II (1000 ng/kg/day) for 28 days. Locomotor activity and cognitive performance were assessed using the open field, Y-maze, and novel object recognition tests. Fluorescently labeled amyloid-beta (Aβ) was injected into the cisterna magna, and cerebral Aβ clearance was evaluated 45 minutes later. Results Blood pressure increased significantly in all groups. Pericyte ablation was associated with reduced locomotor activity in the open field test. Working memory and novel object recognition performance were impaired in hypertensive pericyte ablated mice. Aβ clearance analysis revealed venous localization of Aβ in mice with intact pericytes, whereas pericyte-ablated mice showed widespread parenchymal Aβ retention with impaired venous drainage. Conclusions Pericyte ablation is associated with altered blood pressure regulation, cognitive impairment, and delayed cerebral waste clearance in hypertension. These findings highlight the critical role of pericytes in maintaining vascular-brain homeostasis and suggest their importance in protecting against hypertension-related cognitive decline and dementia. Conflict of interest Funded by TÜBİTAK (The Scientific and Technological Research Council of Turkey), no conflict of interest