Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia.
Aging
Central nervous system
Inflammation
Oxidative stress
Renin-angiotensin system
Journal
The journals of gerontology. Series A, Biological sciences and medical sciences
ISSN: 1758-535X
Titre abrégé: J Gerontol A Biol Sci Med Sci
Pays: United States
ID NLM: 9502837
Informations de publication
Date de publication:
01 04 2022
01 04 2022
Historique:
received:
20
04
2021
pubmed:
17
12
2021
medline:
6
4
2022
entrez:
16
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 34914835
pii: 6463498
doi: 10.1093/gerona/glab376
pmc: PMC8974324
doi:
Substances chimiques
AGTR1 protein, human
0
Amyloid beta-Peptides
0
Receptor, Angiotensin, Type 1
0
Angiotensin II
11128-99-7
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
664-672Subventions
Organisme : NIA NIH HHS
ID : P30 AG066507
Pays : United States
Organisme : Bright Focus Foundation Research Award
Organisme : NIA NIH HHS
ID : K23 AG062807
Pays : United States
Organisme : Nathan W. and Margaret T. Shock Aging Research Foundation
Organisme : Intramural Research Program
Organisme : Nathan Shock Scholar in Aging
Organisme : NIA NIH HHS
ID : P30 AG021334
Pays : United States
Organisme : NIA NIH HHS
ID : R01 AG017917
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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