The association of angiotensin-converting enzyme with biomarkers for Alzheimer’s disease
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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 β 1–42, 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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CSF levels of ACE are associated with Aβ levels and LOAD risk, and ACE can inhibit Aβ toxicity and aggregation.
“cerebrospinal fluid (CSF) levels of the angiotensin-converting enzyme (ACE) are associated with Aβ levels81 and LOAD risk82, and studies show ACE can inhibit Aβ toxicity and aggregation83.”
From Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing (2019) · cites this paper as [81]
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Alzheimer Disease Genetics Consortium (ADGC), Kunkle, B. W., The European Alzheimer’s Disease Initiative (EADI), Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE), Genetic and Environmental Risk in AD/Defining Genetic, P. A. E. R. F. A. D. C. (., Grenier-Boley, B., Sims, R., Bis, J. C., Damotte, V., Naj, A. C., et al. (2019) · Nature Genetics · doi:10.1038/s41588-019-0358-2 · Cited by 2,946 · see citing works
Self-citationGWAS on family history of Alzheimer’s disease
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“In recent years, the relationship between ACE inhibitors and AD has been an active field of study and has resulted in two leading hypotheses of how ACE inhibitors may alter AD risk [34, 39].”
Background
- Authors
- Jochemsen, H. M., Teunissen, C. E., Ashby, E. L., van der Flier, W. M., Jones, R. E., Geerlings, M. I., Scheltens, P., Kehoe, P. G., & Muller, M.
- Affiliations
- University Medical Center Utrecht (NL)
- Amsterdam UMC Location Vrije Universiteit Amsterdam (NL)
- Frenchay Hospital (GB)
- Amsterdam Neuroscience (NL)
- Leiden University Medical Center (NL)
- Corresponding author
- Kehoe, Patrick G
- Muller, Majon
- ORCID
- Venue
- Alzheimer's Research & Therapy
- Published
- 2014-05-15
- Volume
- 6
- Issue
- 3
- Pages
- 27-27
- ISSN
- 1758-9193 (ISSN-L)
- PMC
- PMC4075229
- OpenAlex
- W2155868677
- Cited by
- 77
- References
- 35
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 11 · 2022: 7 · 2021: 10 · 2020: 5 · 2019: 8 · 2018: 6 · 2017: 5 · 2016: 6 · 2015: 4 · 2014: 1
- FWCI
- 3.51
- 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)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Vanderbilt University Medical Center
- University of Bristol
- Internationale Stichting Alzheimer Onderzoek (09502)
- Stichting Dioraphte
- Alzheimer Nederland (WE.15-2011-02)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- angiotensin-converting enzyme, Alzheimer's disease, amyloid-beta, cerebrospinal fluid biomarkers, tau protein, phosphorylated tau, ACE activity, amyloid beta degradation, ACE inhibitors, subjective memory complaints, dementia
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