Angiotensin II type 1 receptor antagonists like losartan have been found to lower the incidence and progression to Alzheimer's disease (AD), as well as rescue cognitive and cerebrovascular deficits in AD mouse models.
These findings have deepened our understanding on the role of Ang II in the pathogenesis of AD and support the use of AT1R antagonists for the treatment of this devastating neurodegenerative disease.
This study aimed to investigate the role of candesartan, an angiotensin II type 1 receptor blocker, in modulation of glial functions associated with AD.
Angiotensin-III (Ang-III) activates the AT1R and angiotensin type-2 receptor (AT2R), but its potential role in the pathophysiology of AD remains unexplored.
The co-administration of angiotensin converting enzyme inhibitors (ACEi) and angiotensin II (AngII) receptor blockers (ARB) that bind angiotensin type 1 receptors (AT1R) may protect from Alzheimer's disease (AD) better than each treatment taken alone.
Together, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of 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.