Open Access 01-06-2014 | Research
The association of angiotensin-converting enzyme with biomarkers for Alzheimer’s disease
Published in: Alzheimer's Research & Therapy | Issue 3/2014
Login to get accessAbstract
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.