title: Angiotensin-converting enzyme (ACE) levels and activity in Alzheimer's disease, and relationship of perivascular ACE-1 to cerebral amyloid angiopathy.
abstract: OBJECTIVE
  Several observations point to the involvement of angiotensin-converting enzyme-1 (ACE-1) in Alzheimer's disease (AD): ACE-1 cleaves amyloid-beta peptide (Abeta) in vitro, the level and activity of ACE-1 are reportedly increased in AD, and variations in the ACE-1 gene are associated with AD. We analysed ACE-1 activity and expression in AD and control brains, particularly in relation to Abeta load and cerebral amyloid angiopathy (CAA).
  
  
  METHODS
  ACE-1 activity was measured in the frontal cortex from 58 control and 114 AD cases of known Abeta load and CAA severity. The distribution of ACE-1 was examined immunohistochemically. In five AD cases with absent or mild CAA, five with moderate to severe CAA and five controls with absent or mild CAA, levels of vascular ACE-1 were assessed by quantitative immunofluorescence.
  
  
  RESULTS
  ACE-1 activity was increased in AD (P < 0.001) and correlated directly with parenchymal Abeta load (P = 0.05). Immunohistochemistry revealed ACE-1 in neurones and cortical blood vessels - in the intima but most abundant perivascularly. Cases with moderate to severe CAA had significantly more vessel-associated ACE-1 than did those with little or no CAA. Perivascular ACE-1 did not colocalize with Abeta, smooth muscle actin, glial fibrillary acidic protein, collagen IV, vimentin or laminin, but was similarly distributed to extracellular matrix (ECM) proteins fibronectin and decorin.
  
  
  CONCLUSIONS
  Our findings indicate that ACE-1 activity is increased in AD, in direct relationship to parenchymal Abeta load. Increased ACE-1, probably of neuronal origin, accumulates perivascularly in severe CAA and colocalizes with vascular ECM. The possible relationship of ACE-1 to the deposition of perivascular ECM remains to be determined.
authors.affiliation: Dementia Research Group, Institute of Clinical Neurosciences, Clinical Science at North Bristol, University of Bristol, Frenchay Hospital, Frenchay, Bristol, UK. scott.miners@bristol.ac.uk
authors.forename: J S
authors.initials: JS
authors.lastname: Miners
authors.forename: E
authors.initials: E
authors.lastname: Ashby
authors.forename: Z
authors.initials: Z
authors.lastname: Van Helmond
authors.forename: K A
authors.initials: KA
authors.lastname: Chalmers
authors.forename: L E
authors.initials: LE
authors.lastname: Palmer
authors.forename: S
authors.initials: S
authors.lastname: Love
authors.forename: P G
authors.initials: PG
authors.lastname: Kehoe
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001808:Blood Vessels / Q000201:enzymology; D001921:Brain / Q000098:blood supply / Q000201:enzymology*; D016657:Cerebral Amyloid Angiopathy / Q000201:enzymology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D007703:Peptidyl-Dipeptidase A