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

Introduction: Lower angiotensin-converting enzyme (ACE) activity could increase the risk of Alzheimer's disease (AD) as ACE functions to degrade amyloid-beta (A beta). Therefore, we investigated whether ACE protein and activity levels in cerebrospinal fluid (CSF) and serum were associated with CSF A beta, 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 beta(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 A beta, indicating more brain A beta 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 A beta. This could suggest that lowering ACE levels by for example ACE-inhibitors might have adverse consequences for patients with, or at risk for AD.