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dc.contributor.authorBurgess, Stephen
dc.contributor.authorGill, Dipender
dc.date.accessioned2022-07-05T09:37:07Z
dc.date.available2022-07-05T09:37:07Z
dc.identifier.issn2376-7839
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/338765
dc.descriptionAbstract Background and Objectives: Angiotensin converting enzyme (ACE) inhibitors are a commonly prescribed class of medication used to treat heart failure, hypertension and chronic kidney disease. However, previous observational studies have shown conflicting directions of associations between ACE inhibitors and risk of Alzheimer’s disease. Genetic evidence has supported a protective effect of cerebral ACE against Alzheimer’s disease (AD). However, it is unclear whether this effect is mediated through blood pressure and extends to other neurodegenerative diseases. Methods: We performed genetic colocalization investigating an effect of cortical ACE expression on AD risk in people of European ancestry. We further investigated whether any effect of ACE expression on AD risk is mediated through changes in blood pressure, and whether effects extend to Parkinson’s disease, small vessel disease or cognitive function in a Mendelian randomization paradigm. Results: There was genetic evidence supporting a protective effect of cortical ACE expression on AD risk in people of European ancestry. Although higher cortical ACE expression was associated with higher blood pressure, there was no strong evidence to support that its association with AD was mediated through blood pressure, nor that ACE expression affected risk of other neurodegenerative traits. Discussion: Genetic evidence supports protective effects of cerebral ACE expression on AD, but not other neurodegenerative outcomes in people of European ancestry. Further work is required to investigate whether therapeutic inhibition of ACE increases risk of Alzheimer’s disease.
dc.description.abstractBackground and Objectives: Angiotensin converting enzyme (ACE) inhibitors are a commonly prescribed class of medication used to treat heart failure, hypertension and chronic kidney disease. However, previous observational studies have shown conflicting directions of associations between ACE inhibitors and risk of Alzheimer’s disease. Genetic evidence has supported a protective effect of cerebral ACE against Alzheimer’s disease (AD). However, it is unclear whether this effect is mediated through blood pressure and extends to other neurodegenerative diseases. Methods: We performed genetic colocalization investigating an effect of cortical ACE expression on AD risk in people of European ancestry. We further investigated whether any effect of ACE expression on AD risk is mediated through changes in blood pressure, and whether effects extend to Parkinson’s disease, small vessel disease or cognitive function in a Mendelian randomization paradigm. Results: There was genetic evidence supporting a protective effect of cortical ACE expression on AD risk in people of European ancestry. Although higher cortical ACE expression was associated with higher blood pressure, there was no strong evidence to support that its association with AD was mediated through blood pressure, nor that ACE expression affected risk of other neurodegenerative traits. Discussion: Genetic evidence supports protective effects of cerebral ACE expression on AD, but not other neurodegenerative outcomes in people of European ancestry. Further work is required to investigate whether therapeutic inhibition of ACE increases risk of Alzheimer’s disease.
dc.description.sponsorshipWellcome Trust and the Royal Society (204623/Z/16/Z); United Kingdom Research and Innovation Medical Research Council (MC_UU_00002/7); National Institute for Health Research Cambridge Biomedical Research Centre (BRC-1215-20014);
dc.formatSBP using the HyPrColoc method1
dc.publisherLippincott, Williams & Wilkins
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectCognitive Disorders/Dementia
dc.subjectAlzheimer's disease
dc.subjectCognitive aging
dc.subjectParkinson's disease with dementia
dc.subjectVascular dementia
dc.titleGenetic evidence for protective effects of angiotensin converting enzyme against Alzheimer's disease but not other neurodegenerative diseases in European populations
dc.typeArticle
dc.publisher.departmentMrc Biostatistics Unit
dc.date.updated2022-06-27T15:46:05Z
prism.publicationNameNeurology Genetics
dc.identifier.doi10.17863/CAM.85779
dcterms.dateAccepted2022-06-17
rioxxterms.versionofrecord10.1212/NXG.0000000000200014
rioxxterms.versionAM
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
datacite.contributor.supervisorBurgess, Stephen
dcterms.formatpdf
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
rioxxterms.typeJournal Article/Review
cam.issuedOnline2022-08-29
cam.orpheus.successMon Jan 23 08:37:41 GMT 2023 - This item is covered by RRS with an embargo. The item is now published and embargo has been lifted.*
cam.orpheus.counter18
cam.depositDate2022-06-27
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement
rioxxterms.freetoread.startdate2025-07-05


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International