Cited by 276Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchGenetic Associations and Epidemiology

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Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease

Kehoe, Patrick G., Russ, Carsten, McIlroy, Stephen, Williams, Hywel, Holmans, Peter, Holmes, Clive, Liolitsa, Danae, Vahidassr, Djamil, Powell, John, McGleenon, Bronagh, Liddell, Malcolm, Plomin, Robert, Dynan, Kevin, Williams, Nigel, Neal, Jim, Cairns, Nigel J., Wilcock, Gordon, Passmore, Peter, Lovestone, Simon, Williams, Julie, Owen, Michael J.·1999·Nature Genetics

DOI 10.1038/5009

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“Mini-mental state”
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An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels
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PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidyl carboxypeptidase 1)
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Genetic associations with human longevity at the APOE and ACE loci
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Apolipoprotein E genotyping by one-stage PCR
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A Prospective Evaluation of an Angiotensin-Converting–Enzyme Gene Polymorphism and the Risk of Ischemic Heart Disease
Lindpaintner, K., Pfeffer, M. A., Kreutz, R. H., Stampfer, M. J., Grodstein, F., Lamotte, F., Buring, J. E., & Hennekens, C. H. (1995) · New England Journal of Medicine · doi:10.1056/nejm199503163321103 · Cited by 899
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Genetic susceptibility to Alzheimer disease
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Attenuation of scopolamine-induced spatial learning impairments by an angiotensin IV analog
Pederson, E. S., Harding, J. W., & Wright, J. W. (1998) · Regulatory Peptides · doi:10.1016/s0167-0115(98)00028-7 · Cited by 103

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Items 101–200 of 276

Connecting the brain cholesterol and renin–angiotensin systems: potential role of statins and RAS ‐modifying medications in dementia
Petek, B., Villa‐Lopez, M., Loera‐Valencia, R., Gereñu, G., Winblad, B. G., Kramberger, M. G., Ismail, M. A. M., Eriksdotter, M., & Ptacek, S. G. (2018) · Journal of Internal Medicine · doi:10.1111/joim.12838 · Cited by 47
Effect of the angiotensin I-converting enzyme I/D polymorphism on cognitive decline☆
Richard, F., Berr, C., Amant, C., Helbecque, N., Amouyel, P., & Alpérovitch, A. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00102-5 · Cited by 42
Diabetes and dementia
Lovestone, S. (1999) · Neurology · doi:10.1212/wnl.53.9.1907 · Cited by 42
Self-citation
Multi-trait association studies discover pleiotropic loci between Alzheimer’s disease and cardiometabolic traits
Program, T. V. M. V., Bone, W. P., Siewert, K. M., Jha, A., Klarin, D., Damrauer, S. M., Chang, K.-M., Tsao, P. S., Assimes, T. L., Ritchie, M. D., et al. (2021) · Alzheimer's Research & Therapy · doi:10.1186/s13195-021-00773-z · Cited by 41
“This locus has also been well studied from an AD perspective [32, 33, 35].”
Background
Catabolic attacks of membrane-bound angiotensin-converting enzyme on the N-terminal part of species-specific amyloid-beta peptides.
Sun, X., Becker, M., Pankow, K., Krause, E., Ringling, M., Beyermann, M., Maul, B., Walther, T., & Siems, W. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.03.058 · Cited by 48
Aβ degradation or cerebral perfusion? Divergent effects of multifunctional enzymes
Miners, J. S., Palmer, J. C., Tayler, H. M., Palmer, L. E., Ashby, E. L., Kehoe, P. G., & Love, S. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00238 · Cited by 43
“A common Alu (indel) insertion(I)/deletion(D) polymorphism (rs 1799752) in intron 16 of the ACE gene was reported to be associated with sporadic AD, the greatest risk being associated with homozygosity of the I allele (Kehoe et al., 1999).”
BackgroundSelf-citation
Two Opposing Functions of Angiotensin-Converting Enzyme (ACE) That Links Hypertension, Dementia, and Aging
Le, D. D., Brown, L., Malik, K., & Murakami, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413178 · Cited by 40
“Two groups conducted population studies that suggested an association with late-onset AD (LOAD) by investigating an insertion/deletion polymorphism of the ACE gene [25,26].”
Background
Review: The renin-angiotensin-aldosterone system and Alzheimer's disease?
Kehoe, P. G. (2003) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.3317/jraas.2003.017 · Cited by 41
“In recent years, this suggestion has been further supported by the interest generated following the first report of a strong association between inheritance of the insertion allele of the ACE1 and increased risk of sporadic late-onset AD.(41)”
BackgroundResultInfluentialSelf-citation
Angiotensin I converting enzyme polymorphism in humans with age-associated memory impairment: relationship with cognitive performance
David Bartrés-faz, A., Junqué, C., Clemente, I. C., López‐Alomar, A., Valveny, N., López-Guillén, A., López, T., Cubells, M. J., & Moral, P. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01349-5 · Cited by 41
Vascular genetic factors and human longevity
Panza, F., D’Introno, A., Colacicco, A. M., Capurso, C. A., Capurso, S. A., Kehoe, P. G., Capurso, A., & Solfrizzi, V. (2004) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2003.12.005 · Cited by 41
Self-citation
Identification of a single nucleotide polymorphism in the choline acetyltransferase gene associated with Alzheimer's disease
Mubumbila, V., Sutter, A., Ptok, U., Heun, R., & Quirin‐Stricker, C. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00955-2 · Cited by 40
Pharmacogenomics for the treatment of dementia
Cacabelos, R. (2002) · Annals of Medicine · doi:10.1080/078538902320772115 · Cited by 40
APOE promoter, ACE1 and CYP46 polymorphisms and β-amyloid in Alzheimer’s disease
Chalmers, K. A., Culpan, D., Kehoe, P. G., Wilcock, G. K., Hughes, A., & Love, S. (2003) · Neuroreport · doi:10.1097/00001756-200401190-00019 · Cited by 39
Self-citation
Functional regulation of Alu element of human angiotensin-converting enzyme gene in neuron cells
Wu, S.-J., Hsieh, T., Kuo, M., Tsai, M.-L., Tsai, K.-L., Chen, C., & Yang, Y. (2013) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2013.01.003 · Cited by 40
An association analysis of Alzheimer disease candidate genes detects an ancestral risk haplotype clade in ACE and putative multilocus association between ACE, A2M, and LRRTM3
Edwards, T. L., Pericak‐Vance, M. A., Gilbert, J. R., Haines, J. L., Martin, E. R., & Ritchie, M. D. (2008) · American Journal of Medical Genetics Part B Neuropsychiatric Genetics · doi:10.1002/ajmg.b.30899 · Cited by 39
“A gene that has been carefully studied for association with LOAD with inconsistent results is angiotensin converting enzyme (ACE) [Chapman et al., 1998; Scacchi et al., 1998; Kehoe et al., 1999; Alvarez et al., 1999a].”
Background
Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer's disease
Monastero, R., Caldarella, R., Mannino, M., Cefalu, A. B., Lopez, G., Noto, D., Camarda, C., Camarda, L. K. C., Notarbartolo, A., Averna, M. R., et al. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)01182-5 · Cited by 38
Common variants of ACE contribute to variable age-at-onset of Alzheimer’s disease
Kehoe, P. G., Katzov, H., Andreasen, N., Gatz, M., Wilcock, G. K., Cairns, N. J., Palmgren, J., Fairé, U. D., Brookes, A. J., Pedersen, N. L., et al. (2004) · Human Genetics · doi:10.1007/s00439-004-1093-y · Cited by 37
“…report that risk for Alzheimer’s disease (AD; MIM 104300) may be influenced by genetic variants of the gene encoding angiotensin I converting enzyme (ACE; MIM 106180; Kehoe et al. 1999), over 20 cohorts from diverse worldwide populations have been tested in replication attempts (Kehoe et al. 2003).”
BackgroundSelf-citation
Association between angiotensin-converting enzyme gene and late onset Alzheimer's disease in Han Chinese
Yang, J. D., Feng, G., Zhang, J., Lin, Z., Shen, T., Breen, G. D., Clair, D. S., & He, L. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)01591-3 · Cited by 37
The Insertion Polymorphism in Angiotensin-Converting Enzyme Gene Associated With the APOE ε4 Allele Increases the Risk of Late-Onset Alzheimer Disease
Wang, B., Jin, F., Yang, Z., Lu, Z., Kan, R., Li, S., Zheng, C., & Wang, L. (2006) · Journal of Molecular Neuroscience · doi:10.1385/jmn:30:3:267 · Cited by 36
A Multi-Center Study of ACE and the Risk of Late-Onset Alzheimer's Disease
Belbin, O., Brown, K., Shi, H., Medway, C., Abraham, R., Passmore, P., Mann, D., Smith, A. D., Holmes, C., McGuinness, B., et al. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-101914 · Cited by 34
“The most frequent haplotype (H1) contained the previously reported AD-associated (‘risk’) ACE indel I allele [22], while the H2 haplotype contained the (‘protective’) D allele [8].”
BackgroundSelf-citation
Renin Angiotensin Aldosterone System Inhibition in Controlling Dementia-Related Cognitive Decline
Ó’Caoimh, R., Kehoe, P. G., & Molloy, D. W. (2014) · Journal of Alzheimer s Disease · doi:10.3233/jad-141284 · Cited by 35
“Numerous genetic associations between the ACE gene and increased risk of AD have been proposed [39, 40].”
BackgroundSelf-citation
Lack of association between polymorphisms in angiotensin-converting-enzyme and methylenetetrahydrofolate reductase genes and normal cognitive ageing in humans
Visscher, P. M., Tynan, M. C., Whiteman, M. C., Pattie, A., White, I., Hayward, C., Wright, A. F., Starr, J. M., Whalley, L. J., & Deary, I. J. (2003) · Neuroscience Letters · doi:10.1016/s0304-3940(03)00691-8 · Cited by 35
Molecular basis of selective amyloid‐β degrading enzymes in Alzheimer's disease
Żukowska, J., Moss, S. J., Subramanian, V., & Acharya, K. R. (2023) · FEBS Journal · doi:10.1111/febs.16939 · Cited by 36
“Evidence for the role of ACE in AD was revealed in the association between mutations and deletions within the ACE encoding DCP1 gene and an individual’s susceptibility to AD [194,195].”
The ACE DD genotype and D-allele are associated with exceptional longevity: A meta-analysis
Garatachea, N., Marin, P. J., & Lucía, A. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.04.001 · Cited by 32
Disease stages and therapeutic hypotheses in two decades of neurodegenerative disease clinical trials
Mortberg, M. A., Vallabh, S. M., & Minikel, E. V. (2022) · Scientific Reports · doi:10.1038/s41598-022-21820-1 · Cited by 35
A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer's disease
Tian, J., Shi, J., Bailey, K. L., Harris, J. M., Pritchard, A. L., Lambert, J., Chartier‐Harlin, M., Pickering-Brown, S. M., Lendon, C. L., & Mann, D. M. A. (2003) · Neuroscience Letters · doi:10.1016/j.neulet.2003.09.072 · Cited by 33
Sequence variation in the proximity of IDE may impact age at onset of both Parkinson disease and Alzheimer disease
Blomqvist, M. E.-L., Silburn, P. A., Buchanan, D. D., Blennow, K., Mellick, G. D., Brookes, A. J., Andreasen, N., Pedersen, N. L., & Prince, J. A. (2004) · Neurogenetics · doi:10.1007/s10048-004-0173-4 · Cited by 31
“For AD, the 4 allele of APOE is a well-defined risk factor [9], and growing evidence suggests that the gene encoding angiotensin converting enzyme (ACE) may also contribute to disease [10, 11].”
Background
Plasma Angiotensin-Converting Enzyme in Alzheimer's Disease
Vardy, E. R. L. C., Rice, P. J., Bowie, P. C. W., Holmes, J. D., Catto, A. J., & Hooper, N. M. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-1002 · Cited by 32
“An association between the insertion (I)/deletion (D) polymorphism in intron 16 of the ACE gene and susceptibility to the development of AD was initially re-ported [12].”
Renin–angiotensin system gene expression and neurodegenerative diseases
Goldstein, B. I., Speth, R. C., & Trivedi, M. S. (2016) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320316666750 · Cited by 31
Genes involved in Alzheimer's disease, a survey of possible candidates
Serretti, A., Artioli, P., Quartesan, R., & Ronchi, D. D. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-7410 · Cited by 32
“Kehoe et al. [234] reported an association between AD and the insertion allele ofaninsertion/deletion(I/D) polymorphism in intron 16 of the DCP1/ACE gene, which encodes ACE.”
Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Rescue Memory Defects inDrosophila-Expressing Alzheimer’s Disease-Related Transgenes Independently of the Canonical Renin Angiotensin System
Lee, S. H., Gomes, S. M., Ghalayini, J., Iliadi, K. G., & Boulianne, G. L. (2020) · eNeuro · doi:10.1523/eneuro.0235-20.2020 · Cited by 30
“, 2012) but contrasts with in vitro studies, demonstrating that ACE-Is lead to increased Ab 42 production and aggregation (Kehoe et al., 1999; Hemming and Selkoe, 2005; Zou et al., 2007; Liu et al., 2014).”
BackgroundResult
Renin‐angiotensin system blockers affect cognitive decline and serum adipocytokines in Alzheimer's disease
Furiya, Y., Ryo, M., Kawahara, M., Kiriyama, T., Morikawa, M., & Ueno, S. (2012) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2012.06.007 · Cited by 30
“A potential relation between ACE and AD was first suggested by human genetic studies, which reported that an insertion/deletion polymorphism within intron 16 of the ACE gene is associated with AD [14].”
Background
Angiotensin converting enzyme insertion/deletion polymorphism in sporadic and familial Alzheimer's disease and longevity
Nacmias, B., Bagnoli, S., Tedde, A., Cellini, E., Bessi, V., Guarnieri, B., Ortensi, L., Piacentini, S., Bracco, L., & Sorbi, S. (2006) · Archives of Gerontology and Geriatrics · doi:10.1016/j.archger.2006.10.011 · Cited by 30
Angiotensin-converting enzyme deletion allele is beneficial for the longevity of Europeans
Petranović, M. Z., Škarić‐Jurić, T., Narančić, N. S., Tomas, Ž., Krajačić, P., Miličić, J., Barbalić, M., & Tomek-Roksandić, S. (2011) · AGE · doi:10.1007/s11357-011-9270-0 · Cited by 29
“…Blood donors from Cambridge 135 241 102 0.53 0.47 Galinsky et al. 1997 >79 2 270 100/170 Cambridge City population (longitudinal study of cognitive function and aging) 87 128 55 0.56 0.44 Kehoe et al. 1999 80.8±4.5 2 111 Not reported Healthy Alzheimer controls (London population) 41 48 22 0.59 0.”
Influential
ACE variants and risk of intracerebral hemorrhage recurrence in amyloid angiopathy
Domingues‐Montanari, S., Hernández‐Guillamón, M., Fernández‐Cadenas, I., Mendióroz, M., Boada, M., Munuera, J., Rovira, À., Maisterra, O., Parés, M., Gutierrez, M., et al. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2010.01.019 · Cited by 31
C677T Methylentetrahydrofulate Reductase and Angiotensin Converting Enzyme Gene Polymorphisms in Patients with Alzheimer’s Disease in Iranian Population
Keikhaee, M. R., Hashemi, S. B., Najmabadi, H., & Noroozıan, M. (2006) · Neurochemical Research · doi:10.1007/s11064-006-9119-6 · Cited by 29
Shifts in angiotensin I converting enzyme insertion allele frequency across Europe: implications for Alzheimer's disease risk
Panza, F. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.8.1159 · Cited by 29
Effect of chronic angiotensin converting enzyme inhibition on spatial memory and anxiety-like behaviours in rats
Jenkins, T. A., & Chai, S. Y. (2006) · Neurobiology of Learning and Memory · doi:10.1016/j.nlm.2006.08.010 · Cited by 29
Abnormal default-mode network in angiotensin converting enzyme D allele carriers with remitted geriatric depression
Wang, Z., Yuan, Y., Bai, F., You, J., Li, L., & Zhang, Z. (2012) · Behavioural Brain Research · doi:10.1016/j.bbr.2012.02.011 · Cited by 30
Alteration of resting brain function by genetic variation in angiotensin converting enzyme in amnestic-type mild cognitive impairment of Chinese Han
Zhang, Z., Deng, L., Bai, F., Shi, Y., Yu, H., Yuan, Y., Wang, K., Jiang, T., Jia, J., & Zhang, Z. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.01.008 · Cited by 28
Ameliorative Effects of a Combination of Baicalin, Jasminoidin and Cholic Acid on Ibotenic Acid-Induced Dementia Model in Rats
Zhang, J., Li, P., Wang, Y., Liu, J., Zhang, Z., Cheng, W., & Wang, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0056658 · Cited by 27
“found at a significantly lower frequency in AD patients than in controls; in contrast, the genotype with a lower ACE expression was found at a significantly higher frequency [46].”
Epidemiology of the mitochondrial DNA 8344A>G mutation for the myoclonus epilepsy and ragged red fibres (MERRF) syndrome
Remes, A. M. (2003) · Journal of Neurology Neurosurgery & Psychiatry · doi:10.1136/jnnp.74.8.1158 · Cited by 27
Valsartan Abolishes Most of the Memory-Improving Effects of Intracerebroventricular Angiotensin II in Rats
Braszko, J. J. (2005) · Clinical and Experimental Hypertension · doi:10.1080/10641960500298723 · Cited by 26
Angiotensin-Converting Enzyme as a Potential Target for Treatment of Alzheimer's Disease: Inhibition or Activation?
Zou, K., & Michikawa, M. (2008) · Reviews in the Neurosciences · doi:10.1515/revneuro.2008.19.4-5.203 · Cited by 27
Imaging Genetics of Brain Longevity and Mental Wellness: The Next Frontier?
Petrella, J. R., Mattay, V. S., & Doraiswamy, P. M. (2008) · Radiology · doi:10.1148/radiol.2461061994 · Cited by 28
Prognostic plasma protein panel for Aβ deposition in the brain in Alzheimer’s disease
Park, J., Han, S.-H., Lee, H., Jeong, H., Byun, M. S., Bae, J., Kim, H., Lee, D. Y., Yi, D., Shin, S. A., et al. (2019) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2019.101690 · Cited by 27
Lipoproteins, Vascular-Related Genetic Factors, and Human Longevity
Panza, F., D’Introno, A., Capurso, C. A., Colacicco, A. M., Seripa, D., Pilotto, A., Santamato, A., Capurso, A., & Solfrizzi, V. (2007) · Rejuvenation Research · doi:10.1089/rej.2007.0537 · Cited by 27
“Different genetic markers likely to be related with CAD, CVD, or AD have been therefore investigated in centenari-ans in various studies.”
Influential
Genetic and environmental factors in vascular dementia: an update of blood brain barrier dysfunction
Srinivasan, V., Braidy, N., Chan, E. K. W., Xu, Y., & Chan, D. K. Y. (2016) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12558 · Cited by 28
“An insertion (I) or deletion (D) polymorphism in intron 16 of the ACE gene has been associated with increased risk for AD.(43,44) In contrast, two small study populations including 41 or 60 VaD patients did not find any significant effect of ACE I/D polymorphism on the risk of VaD.”
Result
Genetic variation in CTNNA3 encoding alpha-3 catenin and Alzheimer's disease
Blomqvist, M. E.-L., Andreasen, N., Bogdanović, N., Blennow, K., Brookes, A. J., & Prince, J. A. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.01.032 · Cited by 27
Angiotensin-converting enzyme and alpha-2-macroglobulin gene polymorphisms are not associated with Alzheimer's disease in Colombian patients
Camelo, D., Arboleda, G., Yunis, J. J., Pardo, R., Arango, G. J., Solano, E., López, L., Hedmont, D., & Arboleda, H. (2003) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2003.10.008 · Cited by 27
Angiotensin-Converting Enzyme Gene Polymorphisms in Patients with Pulmonary Sarcoidosis
Schürmann, M. (2003) · American Journal of PharmacoGenomics · doi:10.2165/00129785-200303040-00002 · Cited by 24
No association between DCP1 genotype and late‐onset Alzheimer disease
Buss, S., Müller‐Thomsen, T., Hock, C., Alberici, A., Binetti, G. G., Nitsch, R. M., Gal, A., & Finckh, U. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10306 · Cited by 24
Genes Related to Vascular Disease (APOE, VLDL-R, DCP-1) and Other Vascular Factors in Late-Life Depression
Cervilla, J. A., Prince, M. J., Joels, S., Russ, C., & Lovestone, S. (2004) · American Journal of Geriatric Psychiatry · doi:10.1097/00019442-200403000-00011 · Cited by 24
Self-citation
Genetic Association between Alzheimer Disease and the Alpha-Synuclein Gene
Matsubara, M., Yamagata, H. D., Kamino, K., Nomura, T., Kohara, K., Kondo, I., & Miki, T. (2001) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000051243 · Cited by 23
ACE genotype and cognitive decline in an African-Caribbean population
Stewart, R. J., Powell, J. F., Prince, M. J., & MANN, A. H. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.02.017 · Cited by 23
Self-citation
Alzheimer's disease: Its diagnosis and pathogenesis
Kril, J. J., & Halliday, G. M. (2001) · International review of neurobiology · doi:10.1016/s0074-7742(01)48016-0 · Cited by 22
Observational Study of Brain Atrophy and Cognitive Decline Comparing a Sample of Community-Dwelling People Taking Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers Over Time
Moran, C., Xie, K., Poh, S., Chew, S. C. J., Beare, R. J., Wang, W., Callisaya, M. L., & Srikanth, V. K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-180943 · Cited by 21
“Post-mortem studies reported an association between angiotensin converting 10 enzyme and Alzheimer’s disease almost 40 years ago [8, 9] and were further supported by 11 angiotensin I-converting enzyme gene association studies at the end of the last century [10].”
Is the ACE I/D polymorphism associated with extreme longevity? A study on a Spanish cohort
Fiuza‐Luces, C., Ruiz, J. R., Rodríguez‐Romo, G., Santiago, C., Gómez‐Gallego, F., Cano-Nieto, A., Garatachea, N., Rodríguez-Moreno, I., Morán, M., & Lucía, A. (2011) · Journal of the Renin-Angiotensin-Aldosterone System · doi:10.1177/1470320310391505 · Cited by 19
Genetic association analysis: lessons from the study of Alzheimers Disease
Brookes, A. J., & Prince, J. A. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.08.017 · Cited by 20
Mini-review: Angiotensin- converting enzyme 1 (ACE1) and the impact for diseases such as Alzheimer’s disease, sarcopenia, cancer, and COVID-19
Bueno, V., & Frasca, D. (2023) · Frontiers in Aging · doi:10.3389/fragi.2023.1117502 · Cited by 19
“For example, it has been shown that ACE1 polymorphisms are correlated with susceptibility to AD (Hu et al., 1999; Kehoe et al., 1999) but the associated mechanisms are still poorly understood.”
Background
ACE I/D polymorphism affects cognitive function and gray-matter volume in amnestic mild cognitive impairment
Zhang, Z., Deng, L., Bai, F., Shi, Y., Yu, H., Yuan, Y., Jiang, T., Jia, J., & Zhang, Z. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.11.032 · Cited by 19
“Some studies have focused on the association of the gene for the angiotensin I converting enzyme (ACE) with AD [4] [28] [50].”
An investigation of ACE as a risk factor for dementia and cognitive decline in the general population
Yip, A. G., Brayne, C., Easton, D., & Rubinsztein, D. C. (2002) · Journal of Medical Genetics · doi:10.1136/jmg.39.6.403 · Cited by 19
Meta-analysis of genetic association with diagnosed Alzheimer’s disease identifies novel risk loci and implicates Abeta, Tau, immunity and lipid processing
Kunkle, B., Grenier-Boley, B., Sims, R., Bis, J., Naj, A., Boland, A., Vronskaya, M., van der Lee, S., Amlie-Wolf, A., Bellenguez, C., et al. (2018) · doi:10.1101/294629 · Cited by 35
Self-citation
MTHFR and ACE gene polymorphisms and risk of vascular and degenerative dementias in the elderly
Pandey, P., Pradhan, S., Modi, D. R., & Mittal, B. (2009) · Brain and Cognition · doi:10.1016/j.bandc.2009.07.007 · Cited by 18
Association between Angiotensin-Converting Enzyme Gene Polymorphism and Alzheimer’s Disease in a Chinese Population
Zhang, J., Li, X., Zhang, Z., Chen, D., Zhao, H.-L., Wu, Y., & Qu, Q.-M. (2005) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000085075 · Cited by 18
“Some studies in different ethnic groups reported an increased frequency of the I allele and I/I, I/D genotypes in AD patients compared with controls [”
Result
Genotyping of the Angiotensin I-Converting Enzyme Gene Insertion/Deletion Polymorphism by the TaqMan Method
Koch, W., Latz, W., Eichinger, M., Ganser, C., Schömig, A., & Kastrati, A. (2005) · Clinical Chemistry · doi:10.1373/clinchem.2005.051656 · Cited by 17
Experimental approaches for altering the expression of Abeta‐degrading enzymes
Loeffler, D. A. (2023) · Journal of Neurochemistry · doi:10.1111/jnc.15762 · Cited by 18
“Some studies have suggested an increased risk for AD in individuals carrying some ACE allelic variants (Hu et al., 1999; Kehoe et al., 1999; Narain et al., 2000), and ACE insertion polymorphism has been associated with a more rapid rate of AD progression (Hsieh et al., 2019).”
Background
Carriers of Heterozygous Loss-of-Function ACE Mutations Are at Risk for Alzheimer’s Disease
Danilov, S. M., Adzhubei, I. A., Kozuch, A. J., Petukhov, P. A., Popova, I. A., Choudhury, A., Sengupta, D., & Dudek, S. M. (2024) · Biomedicines · doi:10.3390/biomedicines12010162 · Cited by 17
“…that the D allele of the ACE gene I/D polymorphism is associated with increased lifespan [6] inspired the hypothesis and subsequent confirmation [5] that the D allele (associated with increased levels of ACE expression [34]) may be protective for the development of AD, while the I allele…”
Background
Polymorphism of the Angiotensin-Converting Enzyme Gene
Um, J., Kim, H., Choi, T.-J., Jin, C.-S., Parl, S.-T., Lee, K., Rhee, H.-S., Lee, K., Lee, Y., Kim, H., et al. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:3:279 · Cited by 17
ACE inhibition actively promotes cell survival by altering gene expression
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Crohn's associated NOD2 gene variants are not involved in determining susceptibility to multiple sclerosis
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Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism Is Not a Major Determining Factor in the Development of Sporadic Alzheimer Disease: Evidence from an Updated Meta-Analysis
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“A study published in 1999 first reported the association between the I/D polymorphism and SAD in a combined sample of three case-control samples from the United Kingdom [11].”
Background
Association of insertion–deletion polymorphism of ACE gene and Alzheimer’s disease in Egyptian patients
Hassanin, O. M., Moustafa, M., & El-Masry, T. M. (2014) · Egyptian Journal of Medical Human Genetics · doi:10.1016/j.ejmhg.2014.06.001 · Cited by 15
“[20], proposed the first study that eported an association between Alzheimer’s disease and the nsertion (I)/deletion (D) polymorphism (indel) in intron 16 f the gene for angiotensin I-converting enzyme (ACE), and he D allele is associated with raised plasma levels of the nzyme [21].”
Background
Pharmacogenetic Study on the Effect of Rivastigmine on PS2 and APOE Genes in Iranian Alzheimer Patients
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Association between an angiotensin-converting enzyme gene polymorphism and Alzheimer’s disease in a Tunisian population
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Genetic Association between the Apolipoprotein E (APOE) Gene and Different Forms of Alzheimer's Disease
Коровайцева, Г. И., Sherbatich, T., Селезнева, Н. В., Si, G., Голимбет, В. Е., Voskresenskaya, N. I., & Rogaev, E. I. (2001) · Russian Journal of Genetics · doi:10.1023/a:1016610727938 · Cited by 14
Alzheimer disease is not associated with polymorphisms in the angiotensinogen and renin genes
Taylor, A., Ezquerra, M., Bagri, G., Yip, A. G., Goumidi, L., Cottel, D., Easton, D. F., Evans, J. G., Xuereb, J. H., Cairns, N. J., et al. (2001) · American Journal of Medical Genetics · doi:10.1002/ajmg.10044 · Cited by 14
Self-citation
Association of angiotensin-converting enzyme functional gene I/D polymorphism with amnestic mild cognitive impairment
Zhang, Z., Deng, L., Yu, H., Shi, Y., Bai, F., Xie, C., Yuan, Y., Jia, J., & Zhang, Z. (2012) · Neuroscience Letters · doi:10.1016/j.neulet.2012.02.074 · Cited by 19
Genetic analysis of indel markers in three loci associated with Parkinson's disease
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N-domain of angiotensin-converting enzyme hydrolyzes human and rat amyloid-β(1-16) peptides as arginine specific endopeptidase potentially enhancing risk of Alzheimer’s disease
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“Specifically, Aβ peptide substrates intended for testing endoproteolytical activity of ACE should be C-amidated in order to better represent the situation when the peptide forms N-terminal part of a longer polypeptide chain (as in the case of Aβ(1-40) or Aβ(1-42)).”
Background
Angiotensin-converting enzyme polymorphisms AND Alzheimer’s disease susceptibility: An updated meta-analysis
Xin, X., Lai, Z.-H., Ding, K.-Q., Zeng, L., & Ma, J. (2021) · PLoS ONE · doi:10.1371/journal.pone.0260498 · Cited by 15
“Hu [23] 1999 Japan Japanese NINCDS-ADRDA, probable 132/257 1799752 7 Kehoe (3 cohorts) [24] 1999 Ireland European descent NINCDS-ADRDA 542/386 1799752 7”
Genetic Biomarkers in Alzheimer’s Disease
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Effects of Blood Pressure Changes on Alzheimer’s Disease
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Association of Angiotensin-Converting Enzyme Insertion(I)/Deletion (D) Genotype in Alzheimer's Disease Patients of North Indian Population
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“A potential relationship between ACE and AD was first suggested by human genetic studies, which reported that an I/D polymorphism within intron 16 of the ACE gene associates with AD (Kehoe et al., 1999).”
Background
Variation in the DCP1 gene, encoding the angiotensin converting enzyme ACE, is not associated with increased susceptibility to Alzheimerʼs disease
Carbonell, J., Allen, R., Kalsi, G., McQuillin, A., Livingston, G., Katona, C., Walker, Z., Katz, A., Rands, G., Stevens, T., et al. (2003) · Psychiatric Genetics · doi:10.1097/00041444-200303000-00008 · Cited by 14
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No contribution of angiotensin-converting enzyme (ACE) gene variants to severe obesity: a model for comprehensive case/control and quantitative cladistic analysis of ACE in human diseases
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Boosting angiotensin-converting enzyme (ACE) in microglia protects against Alzheimer’s disease in 5xFAD mice
Gomez, A. R., Byun, H. R., Wu, S., Muhammad, A. K. M. G., Ikbariyeh, J., Chen, J., Muro, A., Li, L., Bernstein, K. E., Ainsworth, R., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00879-1 · Cited by 13
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Self-citation
Angiotensin-converting enzyme gene insertion-deletion polymorphism is a risk marker for Alzheimer’s disease in a Chinese population: a meta-analysis of case–control studies
Yuan, Y., Piao, J., Ma, K., & Lu, N. (2015) · Journal of Neural Transmission · doi:10.1007/s00702-015-1368-6 · Cited by 9
Absorption of orally administered gentamicin in infants with diarrhea.
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The Role of the Renin-Angiotensin System in Amyloid Metabolism of Alzheimer's Disease.
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Association of PS1 1/2, ACE I/D, and LRP C/T polymorphisms with Alzheimer’s disease in the Chinese population: a meta-analysis of case-control studies
Yang, L., Zhou, H.-Y., Ye, Y.-F., Fan, X., Wang, Y.-J., & Meng, Y. (2015) · Genetics and Molecular Research · doi:10.4238/2015.february.6.5 · Cited by 8
Angiotensin converting enzyme and Alzheimer’s disease
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Crosstalk between angiotensin and the nonamyloidogenic pathway of Alzheimer's amyloid precursor protein
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Angiotensin converting enzyme and Alzheimer's disease
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Angiotensin II does not directly affect Aβ secretion or β-/γ-secretase activity via activation of angiotensin II type 1 receptor
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Angiotensin‐converting enzyme and angiotensin II type 1 receptor gene polymorphisms in children with subacute sclerosing panencephalitis
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“, 1996], Alzheimer disease [Kehoe et al., 1999], Parkinson disease [Mellick et al.”
Background
Arterial aging mediates the effect of TNF-α and ACE polymorphisms on mental health in elderly individuals: insights from IKARIA study
Georgiopoulos, G. A., Chrysohoou, C. A., Errigo, A., Pes, G. M., Metaxa, V., Zaromytidou, M., Skoumas, J., Kariori, M. G., Lazaros, G. A., Vogiatzi, G., et al. (2017) · QJM · doi:10.1093/qjmed/hcx074 · Cited by 7

Authors: Kehoe, P. G., Russ, C., McIlroy, S., Williams, H., Holmans, P., Holmes, C., Liolitsa, D., Vahidassr, D., Powell, J., McGleenon, B., Liddell, M., Plomin, R., Dynan, K., Williams, N., Neal, J., Cairns, N. J., Wilcock, G., Passmore, P., Lovestone, S., Williams, J., & Owen, M. J.
Affiliations: Cardiff University (GB)
Queen's University Belfast (GB)
Medical Research Council (GB)
Frenchay Hospital (GB)
Corresponding author: Owen, Michael J.
ORCID: Kehoe, Patrick G.
Williams, Hywel
Holmans, Peter
Holmes, Clive
Powell, John
Plomin, Robert
Williams, Nigel
Wilcock, Gordon
Passmore, Peter
Lovestone, Simon
Williams, Julie
Owen, Michael J.
Venue: Nature Genetics
Publisher: Springer Science and Business Media LLC
Published: 1999-01
Volume: 21
Issue: 1
Pages: 71-72
ISSN: 1061-4036 (ISSN-L)
1546-1718
DOI: 10.1038/5009
OpenAlex: W2102952062
Cited by: 260
References: 14
Citations by year: 2026: 4 · 2025: 4 · 2024: 6 · 2023: 5 · 2022: 4 · 2021: 9 · 2020: 3 · 2019: 11 · 2018: 7 · 2017: 10 · 2016: 5 · 2015: 5 · 2014: 9 · 2013: 6 · 2012: 10
FWCI: 9.29
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Genetics (publishedVersion)
PubMed (publishedVersion)
Bristol Research (University of Bristol) (publishedVersion)
ORCA Online Research @Cardiff (Cardiff University) (submittedVersion)
Research Portal (King's College London) (submittedVersion)
Research Portal (Queen's University Belfast) (submittedVersion)
Explore Bristol Research (submittedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Keywords: DCP1, ACE, angiotensin-converting enzyme, Alzheimer's disease, genetic susceptibility, genetic association, renin-angiotensin system
MeSH terms: Alleles, Alzheimer Disease, Apolipoproteins E, Cardiovascular Diseases, Genotype, Humans, Peptidyl-Dipeptidase A, Endopeptidases, Genetic Variation, Case-Control Studies, Genetic Predisposition to Disease

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Variation in DCP1, encoding ACE, is associated with susceptibility to Alzheimer disease

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