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Angiotensin-converting enzyme 2 is reduced in Alzheimer's disease in association with increasing amyloid-? and tau pathology.


ABSTRACT: BACKGROUND:Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer's disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1-7 (Ang ??(1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity. METHODS:We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n?=?90) and age-matched non-demented controls (n?=?59) for which we have previous data on ACE-1 activity, amyloid ? (A?) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores. RESULTS:ACE-2 activity was significantly reduced in AD compared with age-matched controls (P?

SUBMITTER: Kehoe PG 

PROVIDER: S-EPMC5123239 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Angiotensin-converting enzyme 2 is reduced in Alzheimer's disease in association with increasing amyloid-β and tau pathology.

Kehoe Patrick Gavin PG   Wong Steffenny S   Al Mulhim Noura N   Palmer Laura Elyse LE   Miners J Scott JS  

Alzheimer's research & therapy 20161125 1


<h4>Background</h4>Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer's disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1-7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to A  ...[more]

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