Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia.
Caglar CosardereliogluLolita S NidadavoluClaudene J GeorgeRuth Marx-RattnerLaura PowellQian-Li XueJing TianJoy SalibEsther S OhLuigi FerruciPervin DincerDavid A BennettJeremy D WalstonPeter M AbadirPublished in: The journals of gerontology. Series A, Biological sciences and medical sciences (2022)
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 (AT1R) 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 AT1R blockers. Brain RAS acts mainly through 3 angiotensin receptors: AT1R, AT2R, and AT4R. 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-β and paired helical filament tau pathologies. Our results show higher protein levels of the pro-inflammatory AT1R and phospho-ERK (pERK) in the brains of AD participants. Brain AT1R levels and pERK correlated with higher oxidative stress, lower cognitive performance, and higher tangle and amyloid-β scores. This study identifies molecular changes in b-RAS and offers insight into the role of b-RAS in AD-related brain pathology.
Keyphrases
- angiotensin ii
- angiotensin converting enzyme
- resting state
- oxidative stress
- white matter
- functional connectivity
- blood pressure
- mild cognitive impairment
- cerebral ischemia
- vascular smooth muscle cells
- cognitive decline
- end stage renal disease
- gene expression
- wild type
- chronic kidney disease
- multiple sclerosis
- dna damage
- physical activity
- cognitive impairment
- newly diagnosed
- working memory
- weight loss
- ejection fraction
- peritoneal dialysis
- prognostic factors
- blood brain barrier
- endoplasmic reticulum stress
- pi k akt
- genome wide
- protein protein