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

Caglar Cosarderelioglu; Lolita S. Nidadavolu; Claudene J. George; Ruth Marx-Rattner; Laura Powell; Qian Li Xue; Jing Tian; Joy Salib; Esther S. Oh; Luigi Ferrucci; Pervin Dincer; David A. Bennett; Jeremy D. Walston; Peter M. Abadir

doi:10.1093/gerona/glab376

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

Caglar Cosarderelioglu, Lolita S. Nidadavolu, Claudene J. George, Ruth Marx-Rattner, Laura Powell, Qian Li Xue, Jing Tian, Joy Salib, Esther S. Oh, Luigi Ferrucci, Pervin Dincer, David A. Bennett, Jeremy D. Walston, Peter M. Abadir

Research output: Contribution to journal › Article › peer-review

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 (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.

Original language	English (US)
Pages (from-to)	664-672
Number of pages	9
Journal	Journals of Gerontology - Series A Biological Sciences and Medical Sciences
Volume	77
Issue number	4
DOIs	https://doi.org/10.1093/gerona/glab376
State	Published - Apr 1 2022

Keywords

Aging
Central nervous system
Inflammation
Oxidative stress
Renin-angiotensin system

ASJC Scopus subject areas

Geriatrics and Gerontology
Aging

Access to Document

10.1093/gerona/glab376

Cite this

Cosarderelioglu, C., Nidadavolu, L. S., George, C. J., Marx-Rattner, R., Powell, L., Xue, Q. L., Tian, J., Salib, J., Oh, E. S., Ferrucci, L., Dincer, P., Bennett, D. A., Walston, J. D., & Abadir, P. M. (2022). Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia. Journals of Gerontology - Series A Biological Sciences and Medical Sciences, 77(4), 664-672. https://doi.org/10.1093/gerona/glab376

Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia. / Cosarderelioglu, Caglar; Nidadavolu, Lolita S.; George, Claudene J. et al.
In: Journals of Gerontology - Series A Biological Sciences and Medical Sciences, Vol. 77, No. 4, 01.04.2022, p. 664-672.

Research output: Contribution to journal › Article › peer-review

Cosarderelioglu, C, Nidadavolu, LS, George, CJ, Marx-Rattner, R, Powell, L, Xue, QL, Tian, J, Salib, J, Oh, ES, Ferrucci, L, Dincer, P, Bennett, DA, Walston, JD & Abadir, PM 2022, 'Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia', Journals of Gerontology - Series A Biological Sciences and Medical Sciences, vol. 77, no. 4, pp. 664-672. https://doi.org/10.1093/gerona/glab376

@article{557c4319bf9b411c9cc23b153e876078,

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

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 (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.",

keywords = "Aging, Central nervous system, Inflammation, Oxidative stress, Renin-angiotensin system",

author = "Caglar Cosarderelioglu and Nidadavolu, {Lolita S.} and George, {Claudene J.} and Ruth Marx-Rattner and Laura Powell and Xue, {Qian Li} and Jing Tian and Joy Salib and Oh, {Esther S.} and Luigi Ferrucci and Pervin Dincer and Bennett, {David A.} and Walston, {Jeremy D.} and Abadir, {Peter M.}",

note = "Publisher Copyright: {\textcopyright} 2021 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.",

year = "2022",

month = apr,

day = "1",

doi = "10.1093/gerona/glab376",

language = "English (US)",

volume = "77",

pages = "664--672",

journal = "Journals of Gerontology - Series A Biological Sciences and Medical Sciences",

issn = "1079-5006",

publisher = "Oxford University Press",

number = "4",

}

TY - JOUR

T1 - Higher Angiotensin II Type 1 Receptor Levels and Activity in the Postmortem Brains of Older Persons with Alzheimer's Dementia

AU - Cosarderelioglu, Caglar

AU - Nidadavolu, Lolita S.

AU - George, Claudene J.

AU - Marx-Rattner, Ruth

AU - Powell, Laura

AU - Xue, Qian Li

AU - Tian, Jing

AU - Salib, Joy

AU - Oh, Esther S.

AU - Ferrucci, Luigi

AU - Dincer, Pervin

AU - Bennett, David A.

AU - Walston, Jeremy D.

AU - Abadir, Peter M.

N1 - Publisher Copyright: © 2021 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.

PY - 2022/4/1

Y1 - 2022/4/1

N2 - 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.

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-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.

KW - Aging

KW - Central nervous system

KW - Inflammation

KW - Oxidative stress

KW - Renin-angiotensin system

UR - http://www.scopus.com/inward/record.url?scp=85128160866&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85128160866&partnerID=8YFLogxK

U2 - 10.1093/gerona/glab376

DO - 10.1093/gerona/glab376

M3 - Article

C2 - 34914835

AN - SCOPUS:85128160866

SN - 1079-5006

VL - 77

SP - 664

EP - 672

JO - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

JF - Journals of Gerontology - Series A Biological Sciences and Medical Sciences

IS - 4

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this