title: The association of angiotensin-converting enzyme with biomarkers for Alzheimer's disease.
abstract: BACKGROUND
  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.
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical center, ZKH 4A.35, PO Box 7057, 1007 MB Amsterdam, the Netherlands ; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Hadassa M
authors.initials: HM
authors.lastname: Jochemsen
authors.affiliation: Department of Clinical Chemistry, Neurological Laboratory, VU University Medical Center, Amsterdam, the Netherlands.
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Ashby
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical center, ZKH 4A.35, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Jones
authors.affiliation: Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: Mirjam I
authors.initials: MI
authors.lastname: Geerlings
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical center, ZKH 4A.35, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol BS16 1LE, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.affiliation: Department of Gerontology and Geriatric Medicine, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Majon
authors.initials: M
authors.lastname: Muller