Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia

Cosarderelioglu C., Nidadavolu L. S., George C. J., Marx-Rattner R., Powell L., Xue Q., ...More

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, vol.77, no.4, pp.664-672, 2022 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 77 Issue: 4
  • Publication Date: 2022
  • Doi Number: 10.1093/gerona/glab376
  • Journal Name: JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Social Sciences Citation Index (SSCI), Scopus, Academic Search Premier, Periodicals Index Online, Abstracts in Social Gerontology, AgeLine, CAB Abstracts, CINAHL, EMBASE, MEDLINE, Psycinfo, Public Affairs Index, Veterinary Science Database
  • Page Numbers: pp.664-672
  • Keywords: Aging, Central nervous system, Inflammation, Oxidative stress, Renin-angiotensin system, CONVERTING ENZYME, SIGNALING PATHWAYS, AT1 RECEPTOR, DISEASE, KINASE, ASSOCIATION, ACTIVATION, EXPRESSION, DOPAMINE, PROTEIN
  • Ankara University Affiliated: No

Abstract

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.