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Cerebrospinal Fluid Changes in the Renin-Angiotensin System in Alzheimer's Disease

Kehoe, PG; Al Mulhim, N; Zetterberg, H; Blennow, K; Miners, JS; (2019) Cerebrospinal Fluid Changes in the Renin-Angiotensin System in Alzheimer's Disease. Journal of Alzheimer’s Disease , 72 (2) pp. 525-535. 10.3233/JAD-190721. Green open access

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Abstract

Observations in autopsied brain tissue indicate that overactivation of the classical renin-angiotensin system (cRAS) and underactivity within regulatory RAS pathways (rRAS) are associated with pathology in Alzheimer’s disease (AD). The primary aim of this study was to investigate whether cerebrospinal fluid (CSF) markers of RAS are altered in AD in relation to established CSF markers of disease pathology (lower Aβ42 and elevated tau) and CSF markers of capillary dysfunction. We studied 40 controls and 40 AD cases grouped according to a biomarker profile (i.e., AD cases t-tau>400 pg/mL, pTau >60 pg/mL, and Aβ42 <550 pg/mL). Angiotensin-II converting enyme-1 (ACE1) and ACE2 enzyme activity was measured using fluorogenic peptide substrates; sPDGFRβ and albumin level by sandwich ELISA; and angiotensin-I (Ang-I), Ang-II, and Ang-(1-7) by direct ELISA. CSF Aβ42, total, and phosphorylated tau levels were previously measured by INNOTEST sandwich ELISA. CSF ACE1 activity was significantly elevated in AD (p = 0.008) and positively correlated with ACE2 in AD (r = 0.420, p = 0.007). CSF ACE1 weakly correlated with t-tau (r = 0.294, p = 0.066) and p-tau (r = 0.329, p = 0.038) but not with Aβ42 in the controls but not in AD. ACE1 correlated positively with sPDGFRβ (r = 0.426, p = 0.007), a marker of pericyte injury, and ACE2 correlated positively with albumin (r = 0.422, p = 0.008), a marker of blood-brain barrier integrity. CSF Ang-I, Ang-II, and Ang-(1-7) levels were unchanged in AD. This cross-sectional CSF study indicates RAS dysfunction in relation to capillary damage in A

Type: Article
Title: Cerebrospinal Fluid Changes in the Renin-Angiotensin System in Alzheimer's Disease
Location: Netherlands
Open access status: An open access version is available from UCL Discovery
DOI: 10.3233/JAD-190721
Publisher version: https://doi.org/10.3233/JAD-190721
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Alzheimer’s disease, angiotensin-II, angiotensin-(1-7), angiotensin-II converting enyme-1 (ACE1), angiotensin-II converting enyme-2 (ACE2), cerebrospinal fluid, renin-angiotensin system
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
URI: https://discovery.ucl.ac.uk/id/eprint/10084060
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