Matches in SemOpenAlex for { <https://semopenalex.org/work/W2551207780> ?p ?o ?g. }
- W2551207780 abstract "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 β (Aβ) 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 < 0.0001) and correlated inversely with levels of Aβ ( r = −0.267, P < 0.001) and phosphorylated tau (p-tau) pathology ( r = −0.327, P < 0.01). ACE-2 was reduced in individuals possessing an APOE ε4 allele ( P < 0.05) and was associated with ACE1 indel polymorphism ( P < 0.05), with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD risk allele. ACE-2 activity correlated inversely with ACE-1 activity ( r = −0.453, P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD ( P < 0.0001). Finally, we show that the ratio of Ang II to Ang (1–7) (a proxy measure of ACE-2 activity indicating conversion of Ang II to Ang (1–7)) is reduced in AD. Conclusions Together, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of AD." @default.
- W2551207780 created "2016-11-30" @default.
- W2551207780 creator A5027119794 @default.
- W2551207780 creator A5037949745 @default.
- W2551207780 creator A5074614864 @default.
- W2551207780 creator A5081236106 @default.
- W2551207780 creator A5090149588 @default.
- W2551207780 date "2016-11-25" @default.
- W2551207780 modified "2023-10-09" @default.
- W2551207780 title "Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology" @default.
- W2551207780 cites W1485797085 @default.
- W2551207780 cites W1520957183 @default.
- W2551207780 cites W1534729967 @default.
- W2551207780 cites W1555597750 @default.
- W2551207780 cites W1586043264 @default.
- W2551207780 cites W1586213696 @default.
- W2551207780 cites W1618236677 @default.
- W2551207780 cites W1776336091 @default.
- W2551207780 cites W1828947725 @default.
- W2551207780 cites W1890520376 @default.
- W2551207780 cites W1895881996 @default.
- W2551207780 cites W1964696346 @default.
- W2551207780 cites W1966030100 @default.
- W2551207780 cites W1966865110 @default.
- W2551207780 cites W1967645451 @default.
- W2551207780 cites W1968954730 @default.
- W2551207780 cites W1969501720 @default.
- W2551207780 cites W1972642912 @default.
- W2551207780 cites W1972725492 @default.
- W2551207780 cites W1973755223 @default.
- W2551207780 cites W1980058856 @default.
- W2551207780 cites W1981132320 @default.
- W2551207780 cites W1988655607 @default.
- W2551207780 cites W1992998861 @default.
- W2551207780 cites W1995817686 @default.
- W2551207780 cites W1996241810 @default.
- W2551207780 cites W1998959104 @default.
- W2551207780 cites W2000040025 @default.
- W2551207780 cites W2004840558 @default.
- W2551207780 cites W2007244994 @default.
- W2551207780 cites W2011112318 @default.
- W2551207780 cites W2013523985 @default.
- W2551207780 cites W2017079501 @default.
- W2551207780 cites W2025672718 @default.
- W2551207780 cites W2031902348 @default.
- W2551207780 cites W2037033420 @default.
- W2551207780 cites W2044936845 @default.
- W2551207780 cites W2047430236 @default.
- W2551207780 cites W2050496951 @default.
- W2551207780 cites W2053431736 @default.
- W2551207780 cites W2055646886 @default.
- W2551207780 cites W2060803759 @default.
- W2551207780 cites W2078027022 @default.
- W2551207780 cites W2085176275 @default.
- W2551207780 cites W2088673900 @default.
- W2551207780 cites W2096898082 @default.
- W2551207780 cites W2101348366 @default.
- W2551207780 cites W2101562374 @default.
- W2551207780 cites W2102952062 @default.
- W2551207780 cites W2104943661 @default.
- W2551207780 cites W2106122924 @default.
- W2551207780 cites W2112430900 @default.
- W2551207780 cites W2112849422 @default.
- W2551207780 cites W2113936500 @default.
- W2551207780 cites W2117630260 @default.
- W2551207780 cites W2119013194 @default.
- W2551207780 cites W2119642994 @default.
- W2551207780 cites W2124963700 @default.
- W2551207780 cites W2125008708 @default.
- W2551207780 cites W2128206934 @default.
- W2551207780 cites W2128228199 @default.
- W2551207780 cites W2143733546 @default.
- W2551207780 cites W2145488319 @default.
- W2551207780 cites W2145492845 @default.
- W2551207780 cites W2146868259 @default.
- W2551207780 cites W2149146712 @default.
- W2551207780 cites W2156653951 @default.
- W2551207780 cites W2158212936 @default.
- W2551207780 cites W2161399617 @default.
- W2551207780 cites W2167384912 @default.
- W2551207780 cites W2168194361 @default.
- W2551207780 cites W2168729080 @default.
- W2551207780 cites W2168782395 @default.
- W2551207780 cites W2411505974 @default.
- W2551207780 cites W4256728580 @default.
- W2551207780 doi "https://doi.org/10.1186/s13195-016-0217-7" @default.
- W2551207780 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5123239" @default.
- W2551207780 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27884212" @default.
- W2551207780 hasPublicationYear "2016" @default.
- W2551207780 type Work @default.
- W2551207780 sameAs 2551207780 @default.
- W2551207780 citedByCount "153" @default.
- W2551207780 countsByYear W25512077802017 @default.
- W2551207780 countsByYear W25512077802018 @default.
- W2551207780 countsByYear W25512077802019 @default.
- W2551207780 countsByYear W25512077802020 @default.
- W2551207780 countsByYear W25512077802021 @default.
- W2551207780 countsByYear W25512077802022 @default.
- W2551207780 countsByYear W25512077802023 @default.
- W2551207780 crossrefType "journal-article" @default.