Enhanced capillary amyloid angiopathy-associated pathology in Tg-SwDI mice with deleted nitric oxide synthase 2.

Published

Journal Article

BACKGROUND AND PURPOSE: 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.

Full Text

Duke Authors

Cited Authors

  • Van Nostrand, WE; Xu, F; Rozemuller, AJM; Colton, CA

Published Date

  • October 2010

Published In

Volume / Issue

  • 41 / 10 Suppl

Start / End Page

  • S135 - S138

PubMed ID

  • 20876489

Pubmed Central ID

  • 20876489

Electronic International Standard Serial Number (EISSN)

  • 1524-4628

Digital Object Identifier (DOI)

  • 10.1161/STROKEAHA.110.595272

Language

  • eng

Conference Location

  • United States