title: Enhanced capillary amyloid angiopathy-associated pathology in Tg-SwDI mice with deleted nitric oxide synthase 2.
abstract: OBJECTIVE
  Cerebral amyloid angiopathy Type 1 is characterized by amyloid β protein deposition along cerebral capillaries and is accompanied by perivascular neuroinflammation and accumulation of phospho-tau protein. Tg-SwDI mice recapitulate capillary amyloid deposition and associated neuroinflammation but lack accumulation of perivascular phospho-tau protein.
  
  
  METHODS
  Tg-SwDI mice were bred onto a nitric oxide synthase 2 gene knockout background and aged for 1 year. Brains were harvested and analyzed using immunohistochemical and quantitative stereological methods to determine the extent of capillary amyloid deposition, perivascular activated microglia, and cell-specific accumulation of phospho-tau protein. Similar methods were also used to compare Tg-SwDI/NOS2(-/-) and human cerebral amyloid angiopathy Type 1 brain tissues.
  
  
  RESULTS
  The absence of nitric oxide synthase 2 gene had no effect on the regional pattern or frequency of capillary cerebral amyloid angiopathy or the numbers of perivascular activated microglia in Tg-SwDI mice. On the other hand, Tg-SwDI/NOS2(-/-) mice accumulated phospho-tau protein in perivascular neurons and activated microglia. Tg-SwDI/NOS2(-/-) mice exhibited a very similar distribution of capillary amyloid, activated microglia, and perivascular phospho-tau protein as seen in human cerebral amyloid angiopathy Type 1.
  
  
  CONCLUSIONS
  These findings indicate that Tg-SwDI/NOS2(-/-) mice more fully recapitulate the pathological changes observed with capillary amyloid in human cerebral amyloid angiopathy Type 1.
authors.affiliation: Department of Neurosurgery, HSC T-12/086, Stony Brook University, Stony Brook, NY 11794-8122, USA. William.VanNostrand@stonybrook.edu
authors.forename: William E
authors.initials: WE
authors.lastname: Van Nostrand
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.forename: Annemieke J M
authors.initials: AJ
authors.lastname: Rozemuller
authors.forename: Carol A
authors.initials: CA
authors.lastname: Colton
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002196:Capillaries / Q000378:metabolism / Q000473:pathology*; D016657:Cerebral Amyloid Angiopathy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D051379:Mice; D008822:Mice, Transgenic; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D052247:Nitric Oxide Synthase Type II