title: Angiotensin-converting enzyme in cerebrospinal fluid and risk of brain atrophy.
abstract: BACKGROUND
  Higher angiotensin-converting enzyme (ACE) activity might increase the risk of Alzheimer's disease by increasing blood pressure, and subsequent development of cerebral small vessel disease (CSVD). Yet, it may also decrease this risk, as it functions to degrade amyloid-β, thereby reducing brain atrophy.
  
  
  OBJECTIVE
  To examine the cross-sectional associations of serum and cerebrospinal fluid (CSF) ACE protein levels and activity with brain atrophy and CSVD in a memory clinic cohort.
  
  
  METHODS
  In 118 subjects from the memory clinic based Amsterdam Dementia Cohort (mean age 66 ± 8 years), ACE protein levels (ng/ml) and activity in CSF and serum were investigated. Poisson regression analyses were used to associate ACE measurements with rated global cortical atrophy, medial temporal lobe atrophy, lacunar infarcts, white matter hyperintensities, and microbleeds on brain MRI.
  
  
  RESULTS
  Higher CSF ACE activity was associated with a reduced risk of global brain atrophy. The relative risk (95% CI) of having global cortical atrophy ≥2 per SD increase in CSF ACE activity was 0.67 (0.49; 0.93). ACE levels were not significantly related to measures of CSVD.
  
  
  CONCLUSIONS
  These results show that high ACE might have protective effects on the brain. This could suggest that ACE inhibitors, which may lower CSF ACE levels, are not preferred as antihypertensive treatment in patients at risk for Alzheimer's disease.
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, 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: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands Department of Epidemiology and Biostatistics, VU University Medical Center, 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, UK.
authors.forename: Emma L
authors.initials: EL
authors.lastname: Ashby
authors.affiliation: Department of Clinical Chemistry, Neurochemistry 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, UK.
authors.forename: Ruth E
authors.initials: RE
authors.lastname: Jones
authors.affiliation: Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
authors.affiliation: Alzheimer Center & Department of Neurology, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
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: Dementia Research Group, Institute of Clinical Neurosciences, School of Clinical Sciences, University of Bristol, Frenchay Hospital, Bristol, UK.
authors.forename: Patrick G
authors.initials: PG
authors.lastname: Kehoe
authors.affiliation: Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
authors.forename: Majon
authors.initials: M
authors.lastname: Muller
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics; D001284:Atrophy / Q000134:cerebrospinal fluid / Q000473:pathology; D001921:Brain / Q000473:pathology*; D001927:Brain Diseases / Q000097:blood / Q000134:cerebrospinal fluid* / Q000473:pathology*; D059345:Cerebral Small Vessel Diseases / Q000201:enzymology; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008569:Memory Disorders / Q000134:cerebrospinal fluid / Q000209:etiology; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000134:cerebrospinal fluid*
chemical_list: D001057:Apolipoproteins E; D007703:Peptidyl-Dipeptidase A
keywords: Alzheimer's disease; angiotensin-converting enzyme; brain atrophy; cerebral small vessel disease; hypertension