PMID- 34914835
OWN - NLM
STAT- MEDLINE
DCOM- 20220405
LR  - 20240214
IS  - 1758-535X (Electronic)
IS  - 1079-5006 (Print)
IS  - 1079-5006 (Linking)
VI  - 77
IP  - 4
DP  - 2022 Apr 1
TI  - Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem 
      Brains of Older Persons with Alzheimer's Dementia.
PG  - 664-672
LID - 10.1093/gerona/glab376 [doi]
AB  - 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-beta 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-beta scores. This study 
      identifies molecular changes in b-RAS and offers insight into the role of b-RAS 
      in AD-related brain pathology.
CI  - (c) 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.
FAU - Cosarderelioglu, Caglar
AU  - Cosarderelioglu C
AUID- ORCID: 0000-0002-7560-1287
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
AD  - Department of Internal Medicine, Division of Geriatrics, Ankara University School 
      of Medicine, Ankara, Turkey.
AD  - Department of Medical Biology, Hacettepe University School of Medicine, Ankara, 
      Turkey.
FAU - Nidadavolu, Lolita S
AU  - Nidadavolu LS
AUID- ORCID: 0000-0003-2433-0728
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - George, Claudene J
AU  - George CJ
AD  - Department of Medicine, Division of Geriatrics, Albert Einstein College of 
      Medicine/Montefiore Medical Center, Bronx, New York, USA.
FAU - Marx-Rattner, Ruth
AU  - Marx-Rattner R
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Powell, Laura
AU  - Powell L
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Xue, Qian-Li
AU  - Xue QL
AUID- ORCID: 0000-0001-8818-7444
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
AD  - Johns Hopkins University Center on Aging and Health, Baltimore, Maryland, USA.
FAU - Tian, Jing
AU  - Tian J
AD  - Department of Biostatistics, Bloomberg School of Public Health, Baltimore, 
      Maryland, USA.
FAU - Salib, Joy
AU  - Salib J
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Oh, Esther S
AU  - Oh ES
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Ferrucci, Luigi
AU  - Ferrucci L
AUID- ORCID: 0000-0002-6273-1613
AD  - National Institute on Aging, National Institutes of Health, Baltimore, Maryland, 
      USA.
FAU - Dincer, Pervin
AU  - Dincer P
AD  - Department of Medical Biology, Hacettepe University School of Medicine, Ankara, 
      Turkey.
FAU - Bennett, David A
AU  - Bennett DA
AUID- ORCID: 0000-0003-3689-554X
AD  - Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, 
      Illinois, USA.
FAU - Walston, Jeremy D
AU  - Walston JD
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
FAU - Abadir, Peter M
AU  - Abadir PM
AD  - Division of Geriatric Medicine and Gerontology, Johns Hopkins University School 
      of Medicine, Baltimore, Maryland, USA.
LA  - eng
GR  - P30 AG066507/AG/NIA NIH HHS/United States
GR  - K23 AG035005/AG/NIA NIH HHS/United States
GR  - K23 AG062807/AG/NIA NIH HHS/United States
GR  - P30 AG021334/AG/NIA NIH HHS/United States
GR  - R01 AG017917/AG/NIA NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - J Gerontol A Biol Sci Med Sci
JT  - The journals of gerontology. Series A, Biological sciences and medical sciences
JID - 9502837
RN  - 0 (AGTR1 protein, human)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Receptor, Angiotensin, Type 1)
RN  - 11128-99-7 (Angiotensin II)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - *Alzheimer Disease/metabolism
MH  - Amyloid beta-Peptides/metabolism
MH  - Angiotensin II
MH  - Autopsy
MH  - *Brain/metabolism
MH  - Humans
MH  - *Receptor, Angiotensin, Type 1/metabolism
PMC - PMC8974324
OTO - NOTNLM
OT  - Aging
OT  - Central nervous system
OT  - Inflammation
OT  - Oxidative stress
OT  - Renin-angiotensin system
EDAT- 2021/12/17 06:00
MHDA- 2022/04/06 06:00
PMCR- 2022/12/16
CRDT- 2021/12/16 17:27
PHST- 2021/04/20 00:00 [received]
PHST- 2021/12/17 06:00 [pubmed]
PHST- 2022/04/06 06:00 [medline]
PHST- 2021/12/16 17:27 [entrez]
PHST- 2022/12/16 00:00 [pmc-release]
AID - 6463498 [pii]
AID - glab376 [pii]
AID - 10.1093/gerona/glab376 [doi]
PST - ppublish
SO  - J Gerontol A Biol Sci Med Sci. 2022 Apr 1;77(4):664-672. doi: 
      10.1093/gerona/glab376.