Chronic Treatment of a Mouse Model of Cerebral Amyloid Angiopathy and Brain AT₁ Receptor Expression

The renin-angiotensin-aldosterone system (RAAS) has been shown to be dysregulated in dementia, with elevated levels of angiotensin-converting enzyme (ACE), angiotensin (Ang) II, and Ang II type 1 receptors (AT₁Rs). Cerebral amyloid angiopathy (CAA), a common cerebrovascular disease, currently has no treatment or cure available. We aimed to determine if a mouse model with CAA (Tg-SwDI) also exhibits elevated levels of AT₁Rs and whether RAAS-targeting drugs (telmisartan and lisinopril) mitigate these effects.

Tg-SwDI mice were treated with sub-depressor doses of either telmisartan or lisinopril from 3-8 months of age, with blood pressure being monitored 2 and 4 months after the start of treatment. Postmortem, receptor autoradiography was performed to determine levels of AT₁R in 13 brain regions in untreated and treated Tg-SwDI mice compared to wild-type controls (C57Bl/6J).

No statistically significant differences among groups were observed in any of the 13 regions analyzed. However, trends with medium to large effect sizes were observed.

CAA did not significantly dysregulate AT₁R levels in the brains of Tg-SwDI mice compared to wild-type mice. Drug treatment caused no significant brain AT₁R alterations. Further studies are required to determine if the trends observed are pathophysiological and pharmacologically significant.