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

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

Research output: Contribution to journalArticle (Academic Journal)peer-review

28 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)27
JournalAlzheimer's Research and Therapy
Volume6
Issue number3
DOIs
Publication statusPublished - 2014

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