@article{05af10c6eeb4449c900f7cb54625395b,
title = "Evaluating the association between genetically proxied ACE inhibition and dementias",
abstract = "Introduction: Angiotensin-converting enzyme (ACE) has been implicated in the metabolism of amyloid beta; however, the causal effect of ACE inhibition on risk of Alzheimer's disease (AD) dementia and other common dementias is largely unknown. Methods: We examined the causal association of genetically proxied ACE inhibition with four types of dementias using a two-sample Mendelian randomization (MR) approach. Results: Genetically proxied ACE inhibition was associated with increased risk of AD dementia (odds ratio per one standard deviation reduction in serum ACE [95% confidence interval]; 1.07 [1.04–1.10], P = 5 × 10−07) and frontotemporal dementia (1.16 [1.04–1.29], P = 0.01) but not with Lewy body dementia or vascular dementia (P > 0.05). These findings were independently replicated and remained consistent in sensitivity analyses. Discussion: This comprehensive MR study provided genetic evidence for an association between ACE inhibition and the risk for AD and frontotemporal dementias. These results should encourage further studies of the neurocognitive effects of ACE inhibition. Highlights: This study evaluated genetically proxied angiotensin-converting enzyme (ACE) inhibition association with dementias. The results suggest an association between ACE inhibition and Alzheimer's disease. The results suggest an association between ACE inhibition and frontotemporal dementia. Those associations can be interpreted as potentially causal.",
keywords = "ACE, Alzheimer's, Mendelian randomization, angiotensin-converting enzyme, angiotensin-converting enzyme inhibitor, dementia, frontotemporal, genomics, neurodegeneration",
author = "Malik Nassan and Iyas Daghlas and Piras, {Ignazio S.} and Emily Rogalski and Reus, {Lianne M.} and Yolande Pijnenburg and Cuddy, {Leah K.} and Richa Saxena and Mesulam, {M. Marsel} and Matt Huentelman",
note = "Funding Information: The authors thank Robert J. Vassar (from Northwestern University) for reviewing the manuscript and providing relevant suggestions. The authors thank Wiesje van der Flier and Sven J. van der Lee for their contribution to the FTD‐R cohort that we used in the replication analysis. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case‐control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco‐fuND FP‐829‐029 (ZonMW projectnumber 733051061). Lianne Reus was funded by the Memorabel fellowship “Identifying biological and clinical relevance of (epi)genetic risk factors in sporadic FTD” (ZonMW projectnumber: 10510022110012). Funding Information: The authors thank Robert J. Vassar (from Northwestern University) for reviewing the manuscript and providing relevant suggestions. The authors thank Wiesje van der Flier and Sven J. van der Lee for their contribution to the FTD-R cohort that we used in the replication analysis. Research of the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. The Alzheimer Center Amsterdam is supported by Stichting Alzheimer Nederland and Stichting VUmc fonds. The clinical database structure was developed with funding from Stichting Dioraphte. Genotyping of the Dutch case-control samples was performed in the context of EADB (European Alzheimer DNA biobank) funded by the JPco-fuND FP-829-029 (ZonMW projectnumber 733051061). Lianne Reus was funded by the Memorabel fellowship “Identifying biological and clinical relevance of (epi)genetic risk factors in sporadic FTD” (ZonMW projectnumber: 10510022110012). Publisher Copyright: {\textcopyright} 2023 the Alzheimer's Association.",
year = "2023",
month = sep,
doi = "https://doi.org/10.1002/alz.13062",
language = "English",
volume = "19",
pages = "3894--3901",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "9",
}