We studied the ability of the AT1 receptor antagonist losartan to cure or prevent AD hallmarks in aged (~18months at endpoint, 3months treatment) or adult (~12months at endpoint, 10months treatment) human amyloid precursor protein (APP) transgenic mice.
Collectively, these results provide a putative link among Abeta toxicity, AT(2) receptor oligomerization, and disruption of the signaling pathway through M(1) mAChR and Galpha(q/11) and potentially contribute to our understanding of the cholinergic deficit observed in AD.
Inhibition of AT2 oligomerization upon stereotactic expression of the AT2 receptor mutant revealed that Galphaq/11-sequestering AT2 oligomers enhanced the development of neurodegenerative symptoms in the hippocampus of transgenic mice with AD-like pathology.