JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, vol.77, no.4, pp.664-672, 2022 (SCI-Expanded)
Aging is a key risk factor in Alzheimer's dementia (AD) development and progression. The primary dementia-protective benefits of angiotensin II subtype 1 receptor (AT(1)R) blockers are believed to arise from systemic effects on blood pressure. However, a brain-specific renin-angiotensin system (b-RAS) exists, which can be altered by AT(1)R blockers. Brain RAS acts mainly through 3 angiotensin receptors: AT(1)R, AT(2)R, and AT(4)R. Changes in these brain angiotensin receptors may accelerate the progression of AD. Using postmortem frontal cortex brain samples of age- and sex-matched cognitively normal individuals (n = 30) and AD patients (n = 30), we sought to dissect the b-RAS changes associated with AD and assess how these changes correlate with brain markers of oxidative stress, inflammation, and mitochondrial dysfunction as well as amyloid-beta and paired helical filament tau pathologies. Our results show higher protein levels of the pro-inflammatory AT(1)R and phospho-ERK (pERK) in the brains of AD participants. Brain AT(1)R levels and pERK correlated with higher oxidative stress, lower cognitive performance, and higher tangle and amyloid-beta scores. This study identifies molecular changes in b-RAS and offers insight into the role of b-RAS in AD-related brain pathology.