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.
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.
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.