As a recently identified bioactive peptide of brain renin-angiotensin system (RAS), angiotensin-(1-7) [Ang-(1-7)] along with its metabolic enzyme angiotensin-converting enzyme (ACE) 2 and its receptor Mas forms ACE2/Ang-(1-7)/Mas axis. Accumulating evidence suggests an essential role of ACE2/Ang-(1-7)/Mas axis in maintaining normal cognitive functions in both animals and human subjects, and dysregulation of this axis contributed to the pathogenesis of several neurodegenerative diseases such as hypertension-induced neurodegeneration and vascular dementia. To date, whether this axis was associated with the etiology and progression of Alzheimer's disease (AD), the most prevalent neurodegenerative disease in the elderly, remains unclear. In the current study, by using senescence-accelerated mouse prone 8 (SAMP8) mice, an animal model of sporadic AD, we showed for the first time that the level of Ang-(1-7) in the brain was significantly reduced during disease progression. More importantly, an inverse correlation was found between Ang-(1-7) level and tau hyperphosphorylation, a pathological hallmark of AD, in cerebral cortex and hippocampus of SAMP8 mice. Meanwhile, this has been further confirmed in P301S mice, an animal model of pure tauopathy. All these findings suggested that Ang-(1-7), the main effector of brain ACE2/Ang-(1-7)/Mas axis, might be implicated in the etiology and progression of AD, possibly via modulation of tau hyperphosphorylation.
Keywords: Alzheimer’s disease; Angiotensin-(1-7); Hyperphosphorylation; P301S mice; SAMP8; Tau.