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Published in: Alzheimer's Research & Therapy 3/2014

Open Access 01-06-2014 | Research

The association of angiotensin-converting enzyme with biomarkers for Alzheimer’s disease

Authors: Hadassa M Jochemsen, Charlotte E Teunissen, Emma L Ashby, Wiesje M van der Flier, Ruth E Jones, Mirjam I Geerlings, Philip Scheltens, Patrick G Kehoe, Majon Muller

Published in: Alzheimer's Research & Therapy | Issue 3/2014

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Abstract

Introduction

Lower angiotensin-converting enzyme (ACE) activity could increase the risk of Alzheimer’s disease (AD) as ACE functions to degrade amyloid-β (Aβ). Therefore, we investigated whether ACE protein and activity levels in cerebrospinal fluid (CSF) and serum were associated with CSF Aβ, total tau (tau) and tau phosphorylated at threonine 181 (ptau).

Methods

We included 118 subjects from our memory clinic-based Amsterdam Dementia Cohort (mean age 66 ± 8 years) with subjective memory complaints (n = 40) or AD (n = 78), who did not use antihypertensive drugs. We measured ACE protein levels (ng/ml) and activity (RFU) in CSF and serum, and amyloid β1–42, tau and ptau (pg/ml) in CSF.

Results

Cross-sectional regression analyses showed that ACE protein level and activity in CSF and serum were lower in patients with AD compared to controls. Lower CSF ACE protein level, and to a lesser extent serum ACE protein level and CSF ACE activity, were associated with lower CSF Aβ, indicating more brain Aβ pathology; adjusted regression coefficients (B) (95% CI) per SD increase were 0.09 (0.04; 0.15), 0.06 (0.00; 0.12) and 0.05 (0.00; 0.11), respectively. Further, lower CSF ACE protein level was associated with lower CSF tau and ptau levels; adjusted B’s (95% CI) per SD increase were 0.15 (0.06; 0.25) and 0.17 (0.10; 0.25), respectively.

Conclusions

These results strengthen the hypothesis that ACE degrades Aβ. This could suggest that lowering ACE levels by for example ACE-inhibitors might have adverse consequences for patients with, or at risk for AD.
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Literature
1.
go back to reference Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E: Alzheimer’s disease. Lancet. 2011, 377: 1019-1031. 10.1016/S0140-6736(10)61349-9.CrossRefPubMed Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, Jones E: Alzheimer’s disease. Lancet. 2011, 377: 1019-1031. 10.1016/S0140-6736(10)61349-9.CrossRefPubMed
2.
go back to reference Rigat B, Hubert C, Henc-Gelas F, Cambien F, Corvol P, Soubrier F: An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990, 86: 1343-1346. 10.1172/JCI114844.PubMedCentralCrossRefPubMed Rigat B, Hubert C, Henc-Gelas F, Cambien F, Corvol P, Soubrier F: An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest. 1990, 86: 1343-1346. 10.1172/JCI114844.PubMedCentralCrossRefPubMed
3.
go back to reference Lehmann DJ, Cortina-Borja M, Warden DR, Smith AD, Sleegers K, Prince JA, van Duijn CM, Kehoe PG: Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol. 2005, 162: 305-317. 10.1093/aje/kwi202.CrossRefPubMed Lehmann DJ, Cortina-Borja M, Warden DR, Smith AD, Sleegers K, Prince JA, van Duijn CM, Kehoe PG: Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol. 2005, 162: 305-317. 10.1093/aje/kwi202.CrossRefPubMed
4.
go back to reference Elkins JS, Douglas VC, Johnston SC: Alzheimer disease risk and genetic variation in ACE: a meta-analysis. Neurology. 2004, 62: 363-368. 10.1212/01.WNL.0000106823.72493.FF.CrossRefPubMed Elkins JS, Douglas VC, Johnston SC: Alzheimer disease risk and genetic variation in ACE: a meta-analysis. Neurology. 2004, 62: 363-368. 10.1212/01.WNL.0000106823.72493.FF.CrossRefPubMed
5.
go back to reference Carrasquillo MM, Zou F, Pankratz VS, Wilcox SL, Ma L, Walker LP, Younkin SG, Younkin CS, Younkin LH, Bisceglio GD, Ertekin-Taner N, Crook JE, Dickson DW, Petersen RC, Graff-Radford NR, Younkin SG: Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer’s disease. Nat Genet. 2009, 41: 192-198. 10.1038/ng.305.PubMedCentralCrossRefPubMed Carrasquillo MM, Zou F, Pankratz VS, Wilcox SL, Ma L, Walker LP, Younkin SG, Younkin CS, Younkin LH, Bisceglio GD, Ertekin-Taner N, Crook JE, Dickson DW, Petersen RC, Graff-Radford NR, Younkin SG: Genetic variation in PCDH11X is associated with susceptibility to late-onset Alzheimer’s disease. Nat Genet. 2009, 41: 192-198. 10.1038/ng.305.PubMedCentralCrossRefPubMed
6.
go back to reference Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, Hosford D, Barnes MR, Briley JD, Borrie M, Coletta N, Delisle R, Dhalla D, Ehm MG, Feldman HH, Fornazzari L, Gauthier S, Goodgame N, Guzman D, Hammond S, Hollingworth P, Hsiung GY, Johnson J, Kelly DD, Keren R, Kertesz A, King KS, Lovestone S, Loy-Englisch I, Matthews PM, et al: Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol. 2008, 65: 45-53.CrossRefPubMed Li H, Wetten S, Li L, St Jean PL, Upmanyu R, Surh L, Hosford D, Barnes MR, Briley JD, Borrie M, Coletta N, Delisle R, Dhalla D, Ehm MG, Feldman HH, Fornazzari L, Gauthier S, Goodgame N, Guzman D, Hammond S, Hollingworth P, Hsiung GY, Johnson J, Kelly DD, Keren R, Kertesz A, King KS, Lovestone S, Loy-Englisch I, Matthews PM, et al: Candidate single-nucleotide polymorphisms from a genomewide association study of Alzheimer disease. Arch Neurol. 2008, 65: 45-53.CrossRefPubMed
7.
go back to reference Belbin O, Brown K, Shi H, Medway C, Abraham R, Passmore P, Mann D, Smith AD, Holmes C, McGuinness B, Craig D, Warden D, Heun R, Kölsch H, Love S, Kalsheker N, Williams J, Owen MJ, Carresquillo M, Younkin S, Morgan K, Kehoe PG: A multi-center study of ACE and the risk of late-onset Alzheimer’s disease. J Alzheimers Dis. 2011, 24: 587-597.PubMedCentralPubMed Belbin O, Brown K, Shi H, Medway C, Abraham R, Passmore P, Mann D, Smith AD, Holmes C, McGuinness B, Craig D, Warden D, Heun R, Kölsch H, Love S, Kalsheker N, Williams J, Owen MJ, Carresquillo M, Younkin S, Morgan K, Kehoe PG: A multi-center study of ACE and the risk of late-onset Alzheimer’s disease. J Alzheimers Dis. 2011, 24: 587-597.PubMedCentralPubMed
8.
go back to reference Hemming ML, Selkoe DJ: Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J Biol Chem. 2005, 280: 37644-37650. 10.1074/jbc.M508460200.PubMedCentralCrossRefPubMed Hemming ML, Selkoe DJ: Amyloid beta-protein is degraded by cellular angiotensin-converting enzyme (ACE) and elevated by an ACE inhibitor. J Biol Chem. 2005, 280: 37644-37650. 10.1074/jbc.M508460200.PubMedCentralCrossRefPubMed
9.
go back to reference Hu J, Igarashi A, Kamata M, Nakagawa H: Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (Aβ); retards Aβ aggregation, deposition, fibril formation; and inhibits cytotoxicity. J Biol Chem. 2001, 276: 47863-47868.PubMed Hu J, Igarashi A, Kamata M, Nakagawa H: Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (Aβ); retards Aβ aggregation, deposition, fibril formation; and inhibits cytotoxicity. J Biol Chem. 2001, 276: 47863-47868.PubMed
10.
go back to reference Oba R, Igarashi A, Kamata M, Nagata K, Takano S, Nakagawa H: The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide. Eur J Neurosci. 2005, 21: 733-740. 10.1111/j.1460-9568.2005.03912.x.CrossRefPubMed Oba R, Igarashi A, Kamata M, Nagata K, Takano S, Nakagawa H: The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide. Eur J Neurosci. 2005, 21: 733-740. 10.1111/j.1460-9568.2005.03912.x.CrossRefPubMed
11.
go back to reference Kehoe PG, Miners S, Love S: Angiotensins in Alzheimer’s disease – friend or foe?. Trends Neurosci. 2009, 32: 619-628. 10.1016/j.tins.2009.07.006.CrossRefPubMed Kehoe PG, Miners S, Love S: Angiotensins in Alzheimer’s disease – friend or foe?. Trends Neurosci. 2009, 32: 619-628. 10.1016/j.tins.2009.07.006.CrossRefPubMed
12.
go back to reference Kehoe PG, Passmore PA: The renin–angiotensin system and antihypertensive drugs in Alzheimer’s disease: current standing of the angiotensin hypothesis?. J Alzheimers Dis. 2012, 30: S251-S268.PubMed Kehoe PG, Passmore PA: The renin–angiotensin system and antihypertensive drugs in Alzheimer’s disease: current standing of the angiotensin hypothesis?. J Alzheimers Dis. 2012, 30: S251-S268.PubMed
13.
go back to reference Kehoe PG, Katzov H, Feuk L, Bennet AM, Johansson B, Wiman B, de Faire U, Cairns NJ, Wilcock GK, Brookes AJ, Blennow K, Prince JA: Haplotypes extending across ACE are associated with Alzheimer’s disease. Hum Mol Genet. 2003, 12: 859-867. 10.1093/hmg/ddg094.CrossRefPubMed Kehoe PG, Katzov H, Feuk L, Bennet AM, Johansson B, Wiman B, de Faire U, Cairns NJ, Wilcock GK, Brookes AJ, Blennow K, Prince JA: Haplotypes extending across ACE are associated with Alzheimer’s disease. Hum Mol Genet. 2003, 12: 859-867. 10.1093/hmg/ddg094.CrossRefPubMed
14.
go back to reference Kauwe JS, Wang J, Mayo K, Morris JC, Fagan AM, Holtzman DM, Goate AM: Alzheimer’s disease risk variants show association with cerebrospinal fluid amyloid beta. Neurogenetics. 2009, 10: 13-17. 10.1007/s10048-008-0150-4.PubMedCentralCrossRefPubMed Kauwe JS, Wang J, Mayo K, Morris JC, Fagan AM, Holtzman DM, Goate AM: Alzheimer’s disease risk variants show association with cerebrospinal fluid amyloid beta. Neurogenetics. 2009, 10: 13-17. 10.1007/s10048-008-0150-4.PubMedCentralCrossRefPubMed
15.
go back to reference Wharton W, Stein JH, Korcarz C, Sachs J, Olson SR, Zetterberg H, Dowling M, Ye S, Gleason CE, Underbakke G, Jacobson LE, Johnson LE, Johnson SC, Sager MA, Asthana S, Carlsson CM: The effects of ramipril in individuals at risk for alzheimer’s disease: results of a pilot clinical trial. J Alzheimers Dis. 2012, 32: 147-156.PubMedCentralPubMed Wharton W, Stein JH, Korcarz C, Sachs J, Olson SR, Zetterberg H, Dowling M, Ye S, Gleason CE, Underbakke G, Jacobson LE, Johnson LE, Johnson SC, Sager MA, Asthana S, Carlsson CM: The effects of ramipril in individuals at risk for alzheimer’s disease: results of a pilot clinical trial. J Alzheimers Dis. 2012, 32: 147-156.PubMedCentralPubMed
16.
go back to reference Gillies LK, Werstiuk ES, Lee RM: Cross-over study comparing effects of treatment with an angiotensin converting enzyme inhibitor and an angiotensin II type 1 receptor antagonist on cardiovascular changes in hypertension. J Hypertens. 1998, 16: 477-486. 10.1097/00004872-199816040-00009.CrossRefPubMed Gillies LK, Werstiuk ES, Lee RM: Cross-over study comparing effects of treatment with an angiotensin converting enzyme inhibitor and an angiotensin II type 1 receptor antagonist on cardiovascular changes in hypertension. J Hypertens. 1998, 16: 477-486. 10.1097/00004872-199816040-00009.CrossRefPubMed
17.
go back to reference Wright JW, Harding JW: Brain renin–angiotensin – a new look at an old system. Prog Neurobiol. 2011, 95: 49-67. 10.1016/j.pneurobio.2011.07.001.CrossRefPubMed Wright JW, Harding JW: Brain renin–angiotensin – a new look at an old system. Prog Neurobiol. 2011, 95: 49-67. 10.1016/j.pneurobio.2011.07.001.CrossRefPubMed
18.
go back to reference McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984, 34: 939-944. 10.1212/WNL.34.7.939.CrossRefPubMed McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology. 1984, 34: 939-944. 10.1212/WNL.34.7.939.CrossRefPubMed
19.
go back to reference Jochemsen HM, Geerlings MI, Visseren FL, Algra A, van der Graaf Y, Muller M: Serum angiotensin-converting enzyme and recurrent vascular events. The SMART-MR study. Atherosclerosis. 2012, 224: 486-491. 10.1016/j.atherosclerosis.2012.07.010.CrossRefPubMed Jochemsen HM, Geerlings MI, Visseren FL, Algra A, van der Graaf Y, Muller M: Serum angiotensin-converting enzyme and recurrent vascular events. The SMART-MR study. Atherosclerosis. 2012, 224: 486-491. 10.1016/j.atherosclerosis.2012.07.010.CrossRefPubMed
20.
go back to reference Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, Franciotta D, Frederiksen JL, Fleming JO, Furlan R, Hintzen RQ, Hughes SG, Johnson MH, Krasulova E, Kuhle J, Magnone MC, Raida C, Rejdak K, Schmidt HK, van Pesch V, Waubant E, Wolf C, Giovannoni G, Hemmer B, Tumani H, Deisenhammer F: A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology. 2009, 73: 1914-1922. 10.1212/WNL.0b013e3181c47cc2.PubMedCentralCrossRefPubMed Teunissen CE, Petzold A, Bennett JL, Berven FS, Brundin L, Comabella M, Franciotta D, Frederiksen JL, Fleming JO, Furlan R, Hintzen RQ, Hughes SG, Johnson MH, Krasulova E, Kuhle J, Magnone MC, Raida C, Rejdak K, Schmidt HK, van Pesch V, Waubant E, Wolf C, Giovannoni G, Hemmer B, Tumani H, Deisenhammer F: A consensus protocol for the standardization of cerebrospinal fluid collection and biobanking. Neurology. 2009, 73: 1914-1922. 10.1212/WNL.0b013e3181c47cc2.PubMedCentralCrossRefPubMed
21.
go back to reference Mulder C, Verwey NA, van der Flier WM, Bouwman FH, Kok A, van Elk EJ, Scheltens P, Blankenstein MA: Amyloid-beta(1–42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin Chem. 2010, 56: 248-253. 10.1373/clinchem.2009.130518.CrossRefPubMed Mulder C, Verwey NA, van der Flier WM, Bouwman FH, Kok A, van Elk EJ, Scheltens P, Blankenstein MA: Amyloid-beta(1–42), total tau, and phosphorylated tau as cerebrospinal fluid biomarkers for the diagnosis of Alzheimer disease. Clin Chem. 2010, 56: 248-253. 10.1373/clinchem.2009.130518.CrossRefPubMed
22.
go back to reference Miners S, Ashby E, Baig S, Harrison R, Tayler H, Speedy E, Prince JA, Love S, Kehoe PG: Angiotensin-converting enzyme levels and activity in Alzheimer’s disease: differences in brain and CSF ACE and association with ACE1 genotypes. Am J Transl Res. 2009, 1: 163-177.PubMedCentralPubMed Miners S, Ashby E, Baig S, Harrison R, Tayler H, Speedy E, Prince JA, Love S, Kehoe PG: Angiotensin-converting enzyme levels and activity in Alzheimer’s disease: differences in brain and CSF ACE and association with ACE1 genotypes. Am J Transl Res. 2009, 1: 163-177.PubMedCentralPubMed
23.
go back to reference Miners JS, Ashby E, Van Helmond Z, Chalmers KA, Palmer LE, Love S, Kehoe PG: Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer’s disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy. Neuropathol Appl Neurobiol. 2008, 34: 181-193. 10.1111/j.1365-2990.2007.00885.x.CrossRefPubMed Miners JS, Ashby E, Van Helmond Z, Chalmers KA, Palmer LE, Love S, Kehoe PG: Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer’s disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy. Neuropathol Appl Neurobiol. 2008, 34: 181-193. 10.1111/j.1365-2990.2007.00885.x.CrossRefPubMed
24.
go back to reference Donders AR, van der Heijden GJ, Stijnen T, Moons KG: Review: a gentle introduction to imputation of missing values. J Clin Epidemiol. 2006, 59: 1087-1091. 10.1016/j.jclinepi.2006.01.014.CrossRefPubMed Donders AR, van der Heijden GJ, Stijnen T, Moons KG: Review: a gentle introduction to imputation of missing values. J Clin Epidemiol. 2006, 59: 1087-1091. 10.1016/j.jclinepi.2006.01.014.CrossRefPubMed
25.
go back to reference Van der Heijden GJ, Donders AR, Stijnen T, Moons KG: Imputation of missing values is superior to complete case analysis and the missing-indicator method in multivariable diagnostic research: a clinical example. J Clin Epidemiol. 2006, 59: 1102-1109. 10.1016/j.jclinepi.2006.01.015.CrossRefPubMed Van der Heijden GJ, Donders AR, Stijnen T, Moons KG: Imputation of missing values is superior to complete case analysis and the missing-indicator method in multivariable diagnostic research: a clinical example. J Clin Epidemiol. 2006, 59: 1102-1109. 10.1016/j.jclinepi.2006.01.015.CrossRefPubMed
26.
go back to reference Lendon CL, Thaker U, Harris JM, McDonagh AM, Lambert JC, Chartier-Harlin MC, Iwatsubo T, Pickering-Brown SM, Mann DM: The angiotensin 1-converting enzyme insertion (I)/deletion (D) polymorphism does not influence the extent of amyloid or tau pathology in patients with sporadic Alzheimer’s disease. Neurosci Lett. 2002, 328: 314-318. 10.1016/S0304-3940(02)00553-0.CrossRefPubMed Lendon CL, Thaker U, Harris JM, McDonagh AM, Lambert JC, Chartier-Harlin MC, Iwatsubo T, Pickering-Brown SM, Mann DM: The angiotensin 1-converting enzyme insertion (I)/deletion (D) polymorphism does not influence the extent of amyloid or tau pathology in patients with sporadic Alzheimer’s disease. Neurosci Lett. 2002, 328: 314-318. 10.1016/S0304-3940(02)00553-0.CrossRefPubMed
27.
go back to reference Sleegers K, den Heijer T, van Dijk EJ, Hofman A, Bertoli-Avella AM, Koudstaal PJ, Breteler MM, van Duijn CM: ACE gene is associated with Alzheimer’s disease and atrophy of hippocampus and amygdala. Neurobiol Aging. 2005, 26: 1153-1159. 10.1016/j.neurobiolaging.2004.09.011.CrossRefPubMed Sleegers K, den Heijer T, van Dijk EJ, Hofman A, Bertoli-Avella AM, Koudstaal PJ, Breteler MM, van Duijn CM: ACE gene is associated with Alzheimer’s disease and atrophy of hippocampus and amygdala. Neurobiol Aging. 2005, 26: 1153-1159. 10.1016/j.neurobiolaging.2004.09.011.CrossRefPubMed
28.
go back to reference Jochemsen HM, Geerlings MI, Grool AM, Vincken KL, Mali WP, van der Graaf Y, Muller M: Angiotensin-converting enzyme and progression of white matter lesions and brain atrophy – the SMART-MR study. J Alzheimers Dis. 2012, 29: 39-49.PubMed Jochemsen HM, Geerlings MI, Grool AM, Vincken KL, Mali WP, van der Graaf Y, Muller M: Angiotensin-converting enzyme and progression of white matter lesions and brain atrophy – the SMART-MR study. J Alzheimers Dis. 2012, 29: 39-49.PubMed
29.
go back to reference Tian M, Zhu D, Xie W, Shi J: Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat brains. FEBS Lett. 2012, 586: 3737-3745. 10.1016/j.febslet.2012.09.004.CrossRefPubMed Tian M, Zhu D, Xie W, Shi J: Central angiotensin II-induced Alzheimer-like tau phosphorylation in normal rat brains. FEBS Lett. 2012, 586: 3737-3745. 10.1016/j.febslet.2012.09.004.CrossRefPubMed
30.
go back to reference Zou K, Maeda T, Watanabe A, Liu J, Liu S, Oba R, Satoh Y, Komano H, Michikawa M: Aβ42-to-Aβ40- and angiotensin-converting activities in different domains of angiotensin-converting enzyme. J Biol Chem. 2009, 284: 31914-31920. 10.1074/jbc.M109.011437.PubMedCentralCrossRefPubMed Zou K, Maeda T, Watanabe A, Liu J, Liu S, Oba R, Satoh Y, Komano H, Michikawa M: Aβ42-to-Aβ40- and angiotensin-converting activities in different domains of angiotensin-converting enzyme. J Biol Chem. 2009, 284: 31914-31920. 10.1074/jbc.M109.011437.PubMedCentralCrossRefPubMed
31.
go back to reference Kehoe PG, Wilcock GK: Is inhibition of the renin–angiotensin system a new treatment option for Alzheimer’s disease?. Lancet Neurol. 2007, 6: 373-378. 10.1016/S1474-4422(07)70077-7.CrossRefPubMed Kehoe PG, Wilcock GK: Is inhibition of the renin–angiotensin system a new treatment option for Alzheimer’s disease?. Lancet Neurol. 2007, 6: 373-378. 10.1016/S1474-4422(07)70077-7.CrossRefPubMed
32.
go back to reference Kehoe PG, Davies NM, Martin RM, Ben Shlomo Y: Associations of angiotensin targeting antihypertensive drugs with mortality and hospitalization in primary care patients with dementia. J Alzheimers Dis. 2012, 33: 999-1008. Kehoe PG, Davies NM, Martin RM, Ben Shlomo Y: Associations of angiotensin targeting antihypertensive drugs with mortality and hospitalization in primary care patients with dementia. J Alzheimers Dis. 2012, 33: 999-1008.
33.
go back to reference Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B: Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ. 2010, 340: b5465-10.1136/bmj.b5465. 10.1136/bmj.b5465.:b5465PubMedCentralCrossRefPubMed Li NC, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B: Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: prospective cohort analysis. BMJ. 2010, 340: b5465-10.1136/bmj.b5465. 10.1136/bmj.b5465.:b5465PubMedCentralCrossRefPubMed
Metadata
Title
The association of angiotensin-converting enzyme with biomarkers for Alzheimer’s disease
Authors
Hadassa M Jochemsen
Charlotte E Teunissen
Emma L Ashby
Wiesje M van der Flier
Ruth E Jones
Mirjam I Geerlings
Philip Scheltens
Patrick G Kehoe
Majon Muller
Publication date
01-06-2014
Publisher
BioMed Central
Published in
Alzheimer's Research & Therapy / Issue 3/2014
Electronic ISSN: 1758-9193
DOI
https://doi.org/10.1186/alzrt257

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