Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology
Open accessAbstract
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.
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Re-analysis of 10 deeply sequenced SMART-Seq2-based scSeq datasets from different regions of the nervous system demonstrated that Ace2 and Tmprss2 expression is almost completely absent from neurons.
“re-analysis of 10 deeply sequenced SMART-Seq2-based scSeq datasets from different regions of the nervous system demonstrated that Ace2 and Tmprss2 expression is almost completely absent from neurons, consistent with prior immunostaining results (52, 53) (Figure S10).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [53]
ACE2 protein in human brain is predominantly or exclusively expressed in vasculature, specifically within pericytes.
“Multiple immunostaining studies reveal that ACE2 protein in the human brain is predominantly or exclusively expressed in vasculature (and specifically expressed within pericytes) (52, 53, 70), and many neurological symptoms associated with CoV-2 infection like stroke or altered consciousness are consistent with an underlying vasculopathy (71-76).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [53]
Recombinant human ACE2 abolished labeling with anti-ACE2 antibody in a previous study in human tissue, demonstrating its specificity.
“Recombinant human ACE2 abolished labeling with this antibody in a previous study in human tissue, further demonstrating its specificity (53).”
From Non-neuronal expression of SARS-CoV-2 entry genes in the olfactory system suggests mechanisms underlying COVID-19-associated anosmia (2020) · cites this paper as [53]
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Cites
Hamming, I., Timens, W., Bulthuis, M., Lely, A., Navis, G., & van Goor, H. (2004) · The Journal of Pathology · doi:10.1002/path.1570 · Cited by 5,676 · see citing works
Donoghue, M., Hsieh, F., Baronas, E., Godbout, K., Gosselin, M. L., Stagliano, N. E., Donovan, M. J., Woolf, B., Robison, K. E., Jeyaseelan, R., et al. (2000) · Circulation Research · doi:10.1161/01.res.87.5.e1 · Cited by 3,084 · see citing works
Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., et al. (2012) · Acta Neuropathologica · doi:10.1007/s00401-011-0910-3 · Cited by 2,992 · cited 1× · see citing works
“Brains had been subjected to detailed neuropathological assessment according to the National Institute on Aging-Alzheimer’s Association guidelines [40], and AD pathology was a sufficient explanation for the dementia in these cases.”
MethodA Human Homolog of Angiotensin-converting Enzyme
Tipnis, S. R., Hooper, N. M., Hyde, R., Karran, E. H., Christie, G., & Turner, A. J. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m002615200 · Cited by 2,032 · see citing works
Systematic meta-analyses of Alzheimer disease genetic association studies: the AlzGene database
Bertram, L., McQueen, M. B., Mullin, K., Blacker, D., & Tanzi, R. E. (2007) · Nature Genetics · doi:10.1038/ng1934 · Cited by 1,857 · see citing works
Angiotensin-(1–7) is an endogenous ligand for the G protein-coupled receptor Mas
Santos, R. A. S., Silva, A. C. S. E., Maric, C., Silva, D. M. R., Machado, R. P., de Buhr, I., Heringer‐Walther, S., Pinheiro, S. V. B., Lopes, M. T., Bäder, M., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1432869100 · Cited by 1,805 · see citing works
Angiotensin-converting enzyme 2 is an essential regulator of heart function
Crackower, M. A., Sarao, R., Oudit, G. Y., Yagil, C., Kozieradzki, I., Scanga, S. E., Oliveira-dos-Santos, A. J., da Costa, J., Zhang, L., Pei, Y., et al. (2002) · Nature · doi:10.1038/nature00786 · Cited by 1,733 · see citing works
Forette, F., Seux, M.-L., Staessen, J. A., Thijs, L., Birkenhäger, W. H., Babarskiene, M.-R., Babeanu, S., Bossini, A., Gil-Extremera, B., Girerd, X., et al. (1998) · The Lancet · doi:10.1016/s0140-6736(98)03086-4 · Cited by 1,441 · see citing works
Hydrolysis of Biological Peptides by Human Angiotensin-converting Enzyme-related Carboxypeptidase
Vickers, C., Hales, P., Kaushik, V. K., Dick, L. R., Gavin, J. M., Tang, J., Godbout, K., Parsons, T. F., Baronas, E., Hsieh, F., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m200581200 · Cited by 1,406 · see citing works
Apolipoprotein E genotyping by one-stage PCR
Wenham, P. R., Price, W. H., & Blundell, G. (1991) · The Lancet · doi:10.1016/0140-6736(91)92823-k · Cited by 1,070 · see citing works
(2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.9.1069 · Cited by 988 · see citing works
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · see citing works
Apolipoprotein E ϵ4 and cerebral hemorrhage associated with amyloid angiopathy
Greenberg, S. M., Rebeck, G. W., Vonsattel, J. P., Gómez‐Isla, T., & Hyman, B. T. (1995) · Annals of Neurology · doi:10.1002/ana.410380219 · Cited by 540 · see citing works
Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease
Li, H., Wetten, S., Li, L., St. Jean, P. L., Upmanyu, R., Surh, L., Hosford, D., Barnes, M. R., Briley, J. D., Borrie, M., et al. (2008) · Archives of Neurology · doi:10.1001/archneurol.2007.3 · Cited by 499 · see citing works
Li, N.-C., Lee, A., Whitmer, R. A., Kivipelto, M., Lawler, E., Kazis, L. E., & Wolozin, B. (2010) · BMJ · doi:10.1136/bmj.b5465 · Cited by 486 · see citing works
Recent advances in the angiotensin‐converting enzyme 2–angiotensin(1–7)–Mas axis
Santos, R. A. S., Ferreira, A. J., & Silva, A. C. S. E. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2008.042002 · Cited by 433 · see citing works
Doobay, M. F., Talman, L. S., Obr, T. D., Tian, X., Davisson, R. L., & Lazartigues, E. D. (2006) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00292.2006 · Cited by 407 · see citing works
Ferrario, C. M., Trask, A. J., & Jessup, J. A. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00618.2005 · Cited by 385 · see citing works
Santos, R. A. S., Campagnole‐Santos, M. J., & Andrade, S. P. (2000) · Regulatory Peptides · doi:10.1016/s0167-0115(00)00138-5 · Cited by 382 · see citing works
Wang, J., Ho, L., Chen, L., Zhao, Z., Zhao, W., Qian, X., Humala, N., Seror, I., Bartholomew, S. R., Rosendorff, C., et al. (2007) · Journal of Clinical Investigation · doi:10.1172/jci31547 · Cited by 331 · see citing works
Angiotensin‐converting enzyme 2 in the brain: properties and future directions
Xia, H., & Lazartigues, E. D. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2008.05723.x · Cited by 321 · see citing works
ACE2/ANG-(1–7)/Mas pathway in the brain: the axis of good
Xu, P., Sriramula, S., & Lazartigues, E. D. (2010) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00222.2010 · Cited by 284 · see citing works
Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease
Kehoe, P. G., Russ, C., McIlroy, S., Williams, H., Holmans, P., Holmes, C., Liolitsa, D., Vahidassr, D., Powell, J., McGleenon, B., et al. (1999) · Nature Genetics · doi:10.1038/5009 · Cited by 260 · cited 3× · see citing works
“(rs1799752) is a genetic risk factor for sporadic AD [17].”
BackgroundInfluentialSelf-citationBrain renin-angiotensin—A new look at an old system
Wright, J. W., & Harding, J. W. (2011) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2011.07.001 · Cited by 233 · see citing works
The brain renin–angiotensin system: a diversity of functions and implications for CNS diseases
Wright, J. W., & Harding, J. W. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-012-1102-2 · Cited by 218 · see citing works
Olichney, J. M., Hansen, L. A., Galasko, D., Saitoh, T., Hofstetter, C. R., Katzman, R., & Thal, L. J. (1996) · Neurology · doi:10.1212/wnl.47.1.190 · Cited by 216 · see citing works
Davies, N. M., Kehoe, P. G., Ben-Shlomo, Y., & Martin, R. M. (2011) · Journal of Alzheimer’s Disease · doi:10.3233/jad-2011-110347 · Cited by 212 · see citing works
Self-citationLehmann, D. J., Cortina-Borja, M., Warden, D. R., Smith, A. D., Sleegers, K., Prince, J. A., van Duijn, C. M., & Kehoe, P. G. (2005) · American Journal of Epidemiology · doi:10.1093/aje/kwi202 · Cited by 199 · see citing works
Self-citationCerebroprotection by angiotensin-(1-7) in endothelin-1-induced ischaemic stroke
Mecca, A. P., Regenhardt, R. W., O’Connor, T. E., Joseph, J. P., Raizada, M. K., Katovich, M. J., & Sumners, C. (2011) · Experimental Physiology · doi:10.1113/expphysiol.2011.058578 · Cited by 197 · see citing works
Brain renin angiotensin in disease
Phillips, M. I., & de Oliveira, E. M. (2008) · Journal of Molecular Medicine · doi:10.1007/s00109-008-0331-5 · Cited by 196 · see citing works
Tsukuda, K., Mogi, M., Iwanami, J., Min, L., Sakata, A., Jing, F., Iwai, M., & Horiuchi, M. (2009) · Hypertension · doi:10.1161/hypertensionaha.109.136879 · Cited by 192 · see citing works
ACE2 overexpression in the paraventricular nucleus attenuates angiotensin II-induced hypertension
Sriramula, S., Cardinale, J. P., Lazartigues, E. D., & Francis, J. (2011) · Cardiovascular Research · doi:10.1093/cvr/cvr242 · Cited by 186 · see citing works
Gallagher, P. E., Chappell, M. C., Ferrario, C. M., & Tallant, E. A. (2005) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00409.2004 · Cited by 185 · see citing works
Angiotensins in Alzheimer's disease – friend or foe?
Kehoe, P. G., Miners, J. S., & Love, S. (2009) · Trends in Neurosciences · doi:10.1016/j.tins.2009.07.006 · Cited by 166 · see citing works
Self-citation(2009) · PubMed Central · Cited by 165 · see citing works
Miners, J. S., Ashby, E., Helmond, Z. V., Chalmers, K. A., Palmer, L. E., Love, S., & Kehoe, P. G. (2007) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.2007.00885.x · Cited by 165 · see citing works
Self-citationProtective Effects of Intranasal Losartan in the APP/PS1 Transgenic Mouse Model of Alzheimer Disease
Danielyan, L., Klein, R., Hanson, L. R., Buadze, M., Schwab, M. G., Gleiter, C. H., & Frey, W. H. (2010) · Rejuvenation Research · doi:10.1089/rej.2009.0944 · Cited by 158 · see citing works
Chalmers, K., Wilcock, G. K., & Love, S. (2003) · Neuropathology and Applied Neurobiology · doi:10.1046/j.1365-2990.2003.00457.x · Cited by 156 · see citing works
The ANG-(1–7)/ACE2/mas axis in the regulation of nephron function
Ferrario, C. M., & Varagić, J. (2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00110.2010 · Cited by 151 · see citing works
Angiotensin-Converting Enzyme 2: Central Regulator for Cardiovascular Function
Xia, H., & Lazartigues, E. D. (2010) · Current Hypertension Reports · doi:10.1007/s11906-010-0105-7 · Cited by 149 · see citing works
Jiang, T., Gao, L., Guo, J., Lu, J., Wang, Y., & Zhang, Y. (2012) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2012.02105.x · Cited by 148 · see citing works
Dong, Y., Kataoka, K., Tokutomi, Y., Nako, H., Nakamura, T., Toyama, K., Sueta, D., Koibuchi, N., Yamamoto, E., Ogawa, H., et al. (2011) · The FASEB Journal · doi:10.1096/fj.11-182873 · Cited by 142 · see citing works
Feng, Y., Yue, X., Xia, H., Bindom, S. M., Hickman, P. J., Filipeanu, C. M., Wu, G., & Lazartigues, E. D. (2008) · Circulation Research · doi:10.1161/circresaha.107.169110 · Cited by 141 · see citing works
Ongali, B., Nicolakakis, N., Tong, X., Aboulkassim, T., Papadopoulos, P., Rosa‐Neto, P., Lecrux, C., Imboden, H., & Hamel, É. (2014) · Neurobiology of Disease · doi:10.1016/j.nbd.2014.04.018 · Cited by 135 · see citing works
Angiotensin-(1–7) enhances LTP in the hippocampus through the G-protein-coupled receptor Mas
Hellner, K., Walther, T., Schubert, M., & Albrecht, D. (2005) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2005.03.012 · Cited by 131 · see citing works
ACE2-Ang-(1-7)-Mas Axis in Brain: A Potential Target for Prevention and Treatment of Ischemic Stroke
Jiang, T., Gao, L., Lu, J., & Zhang, Y. (2013) · Current Neuropharmacology · doi:10.2174/1570159x11311020007 · Cited by 125 · see citing works
Haplotypes extending across ACE are associated with Alzheimer's disease
Kehoe, P. G. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg094 · Cited by 119 · see citing works
Self-citationAlzheimer disease risk and genetic variation in ACE
Elkins, J. S., Douglas, V. C., & Johnston, S. C. (2004) · Neurology · doi:10.1212/01.wnl.0000106823.72493.ff · Cited by 108 · see citing works
Central Angiotensin II Stimulation Promotes β Amyloid Production in Sprague Dawley Rats
Zhu, D., Shi, J., Zhang, Y., Wang, B., Liu, W., Chen, Z., & Tong, Q. (2011) · PLoS ONE · doi:10.1371/journal.pone.0016037 · Cited by 107 · see citing works
Xia, H., Feng, Y., Obr, T. D., Hickman, P. J., & Lazartigues, E. D. (2009) · Hypertension · doi:10.1161/hypertensionaha.108.123844 · Cited by 105 · see citing works
Kume, K., Hanyu, H., Sakurai, H., Takada, Y., Onuma, T., & Iwamoto, T. (2011) · Geriatrics and gerontology international/Geriatrics & gerontology international · doi:10.1111/j.1447-0594.2011.00746.x · Cited by 99 · see citing works
Yamada, K., Uchida, S., Takahashi, S., Takayama, M., Nagata, Y., Suzuki, N., Shirakura, S., & Kanda, T. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.006 · Cited by 98 · see citing works
Central angiotensin II‐induced Alzheimer‐like tau phosphorylation in normal rat brains
Tian, M., Zhu, D., Xie, W., & Shi, J. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.09.004 · Cited by 97 · see citing works
Neuronal over-expression of ACE2 protects brain from ischemia-induced damage
Chen, J., Zhao, Y., Chen, S., Wang, J., Xiao, X., Ma, X., Penchikala, M., Xia, H., Lazartigues, E. D., Zhao, B., et al. (2014) · Neuropharmacology · doi:10.1016/j.neuropharm.2014.01.004 · Cited by 96 · see citing works
Exercise training normalizes ACE and ACE2 in the brain of rabbits with pacing-induced heart failure
Kar, S., Gao, L., & Zucker, I. H. (2010) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00840.2009 · Cited by 95 · see citing works
Angiotensin-(1–7)/Mas axis integrity is required for the expression of object recognition memory
Lazaroni, T. L. D. N., Raslan, A. C. S., Fontes, W. R. P., Oliveira, M. L., Bäder, M., Alenina, N. V., Moraes, M. F. D., Santos, R. A. S., & Pereira, G. S. (2011) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2011.10.003 · Cited by 86 · see citing works
Igase, M., Kohara, K., Nagai, T., Miki, T., & Ferrario, C. M. (2008) · Hypertension Research · doi:10.1291/hypres.31.553 · Cited by 85 · see citing works
Zheng, J., Li, G., Chen, S., Bihl, J. C., Buck, J., Zhu, Y., Xia, H., Lazartigues, E. D., Chen, Y., & Olson, J. E. (2014) · Neuroscience · doi:10.1016/j.neuroscience.2014.04.060 · Cited by 84 · see citing works
ACE and ACE2: their role to balance the expression of angiotensin II and angiotensin-(1–7)
Chappel, M., & Ferrario, C. M. (2006) · Kidney International · doi:10.1038/sj.ki.5000321 · Cited by 81 · see citing works
Jiang, T., Zhang, Y., Zhou, J., Zhu, X., Tian, Y., Zhao, H.-D., Lu, H., Gao, Q., Tan, L., & Yu, J. (2015) · Molecular Neurobiology · doi:10.1007/s12035-015-9260-9 · Cited by 79 · see citing works
Angiotensin-(1-7): A Novel Peptide to Treat Hypertension and Nephropathy in Diabetes?
Shi, R. S. P. Y., & Lo, C. (2015) · Journal of Diabetes & Metabolism · doi:10.4172/2155-6156.1000615 · Cited by 76 · see citing works
Cholinesterase inhibitors reduce cortical Aβ in dementia with Lewy bodies
Ballard, C. G., Chalmers, K. A., Todd, C. E. C., McKeith, I. G., O'Brien, J. T., Wilcock, G. K., Love, S., & Perry, E. K. (2007) · Neurology · doi:10.1212/01.wnl.0000261920.03297.64 · Cited by 67 · see citing works
Liu, S., Liu, J., Miura, Y., Tanabe, C., Maeda, T., Terayama, Y., Turner, A. J., Zou, K., & Komano, H. (2014) · Journal of Neuroscience Research · doi:10.1002/jnr.23404 · Cited by 63 · see citing works
Xiao, L., Gao, L., Lazartigues, E. D., & Zucker, I. H. (2011) · Hypertension · doi:10.1161/hypertensionaha.111.176636 · Cited by 62 · see citing works
Kawajiri, M., Mogi, M., Higaki, N., Matsuoka, T., Ohyagi, Y., Tsukuda, K., Kohara, K., Horiuchi, M., Miki, T., & Kira, J.-I. (2008) · Multiple Sclerosis Journal · doi:10.1177/1352458508097923 · Cited by 61 · see citing works
Ashby, E. L., & Kehoe, P. G. (2013) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2013.812631 · Cited by 54 · see citing works
Self-citationElased, K. M., Cunha, T. S., Marcondes, F. K., & Morris, M. (2008) · Experimental Physiology · doi:10.1113/expphysiol.2007.040311 · Cited by 53 · see citing works
APOE and cerebral amyloid angiopathy in the elderly
Love, S., Nicoll, J. A. R., Hughes, A., & Wilcock, G. K. (2003) · Neuroreport · doi:10.1097/00001756-200308060-00027 · Cited by 52 · see citing works
Angiotensin‐converting enzyme 2: a new target for neurogenic hypertension
Feng, Y., Xia, H., Santos, R. A. S., Speth, R. C., & Lazartigues, E. D. (2009) · Experimental Physiology · doi:10.1113/expphysiol.2009.047407 · Cited by 50 · see citing works
Zou, K., Liu, J., Watanabe, A., Hiraga, S., Liu, S., Tanabe, C., Maeda, T., Terayama, Y., Takahashi, S., Michikawa, M., et al. (2013) · American Journal Of Pathology · doi:10.1016/j.ajpath.2013.01.053 · Cited by 47 · see citing works
Iwanami, J., Mogi, M., Tsukuda, K., et al. (2014) · Hypertension Research · doi:10.1038/hr.2014.49 · Cited by 44 · see citing works
ACE variants and association with brain Aβ levels in Alzheimer's disease.
Miners, J. S., Helmond, Z. V., Raiker, M., Love, S., & Kehoe, P. G. (2010) · PubMed Central · Cited by 43 · see citing works
Self-citationHelmond, Z. V., Miners, J. S., Kehoe, P. G., & Love, S. (2010) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00374.x · Cited by 41 · see citing works
Self-citationCholinesterase inhibitors may increase phosphorylated tau in Alzheimer’s disease
Chalmers, K. A., Wilcock, G. K., Vinters, H. V., Perry, E. K., Perry, R., Ballard, C. G., & Love, S. (2009) · Journal of Neurology · doi:10.1007/s00415-009-5000-2 · Cited by 35 · see citing works
(2010) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.zh2-6109-corr.2010 · Cited by 1 · see citing works
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Gironacci, M. M., Vicario, A., Cerezo, G., & Silva, M. G. (2018) · Clinical Science · doi:10.1042/cs20180189 · Cited by 60 · see citing works
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Tikhonova, M. A., Amstislavskaya, T. G., Belichenko, V. M., Fedoseeva, L. A., Kovalenko, S. P., Pisareva, E. E., Avdeeva, A. S., Kolosova, N. G., Belyaev, N. D., & Aftanas, L. I. (2018) · BMC Neuroscience · doi:10.1186/s12868-018-0412-5 · Cited by 30 · see citing works
- Authors
- Kehoe, P. G., Wong, S., AL Mulhim, N., Palmer, L. E., & Miners, J. S.
- Affiliations
- Southmead Hospital (GB)
- Corresponding author
- Kehoe, Patrick Gavin
- Miners, J. Scott
- Venue
- Alzheimer's Research & Therapy
- Published
- 2016-11-25
- Volume
- 8
- Issue
- 1
- Pages
- 50-50
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC5123239
- OpenAlex
- W2551207780
- Cited by
- 203
- References
- 75
- Citations by year
- 2026: 7 · 2025: 17 · 2024: 13 · 2023: 33 · 2022: 27 · 2021: 46 · 2020: 38 · 2019: 6 · 2018: 12 · 2017: 4
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Alzheimer s Research & Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Bristol Research (University of Bristol) (publishedVersion, cc-by)
- Explore Bristol Research (submittedVersion, cc-by)
- Funders
- Alzheimer's Society
- University of Bristol
- Medical Research Council
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, angiotensin-converting enzyme 2, renin-angiotensin system, angiotensin II, angiotensin-(1-7), amyloid-beta, tau phosphorylation, APOE ε4, cerebral amyloid angiopathy, postmortem brain
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Analysis of Variance, Angiotensin I, Angiotensin II, Apolipoproteins E, Autopsy, Brain, Female, Humans, Peptidyl-Dipeptidase A, Male, Peptide Fragments, Statistics as Topic, Cohort Studies, Case-Control Studies, Amyloid beta-Peptides, tau Proteins, Polymorphism, Single Nucleotide
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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