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.
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 humancerebral 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 humancerebral amyloid angiopathy Type 1. CONCLUSIONS: These findings indicate that Tg-SwDI/NOS2(-/-) mice more fully recapitulate the pathological changes observed with capillary amyloid in humancerebral amyloid angiopathy Type 1.
Authors: Jianting Miao; Feng Xu; Judianne Davis; Irene Otte-Höller; Marcel M Verbeek; William E Van Nostrand Journal: Am J Pathol Date: 2005-08 Impact factor: 4.307
Authors: D A Wink; K M Miranda; M G Espey; R M Pluta; S J Hewett; C Colton; M Vitek; M Feelisch; M B Grisham Journal: Antioxid Redox Signal Date: 2001-04 Impact factor: 8.401
Authors: J M Long; A N Kalehua; N J Muth; J M Hengemihle; M Jucker; M E Calhoun; D K Ingram; P R Mouton Journal: J Neurosci Methods Date: 1998-10-01 Impact factor: 2.390
Authors: Judianne Davis; Feng Xu; Rashid Deane; Galina Romanov; Mary Lou Previti; Kelly Zeigler; Berislav V Zlokovic; William E Van Nostrand Journal: J Biol Chem Date: 2004-02-25 Impact factor: 5.157
Authors: Donna M Wilcock; Matthew R Lewis; William E Van Nostrand; Judianne Davis; Mary Lou Previti; Nastaran Gharkholonarehe; Michael P Vitek; Carol A Colton Journal: J Neurosci Date: 2008-02-13 Impact factor: 6.167
Authors: M P Vitek; D J Christensen; D Wilcock; J Davis; W E Van Nostrand; F Q Li; C A Colton Journal: Neurodegener Dis Date: 2012-02-09 Impact factor: 2.977
Authors: Le Zhang; Kalavathi Dasuri; Sun-Ok Fernandez-Kim; Annadora J Bruce-Keller; Linnea R Freeman; Jennifer K Pepping; Tina L Beckett; M Paul Murphy; Jeffrey N Keller Journal: Biochim Biophys Acta Date: 2013-01-09
Authors: Carol A Colton; Joan G Wilson; Angela Everhart; Donna M Wilcock; Jukka Puoliväli; Taneli Heikkinen; Juho Oksman; Olli Jääskeläinen; Kimmo Lehtimäki; Teemu Laitinen; Nina Vartiainen; Michael P Vitek Journal: J Neuropathol Exp Neurol Date: 2014-08 Impact factor: 3.685
Authors: Xiaoyue Zhu; Joshua Hatfield; Joseph K Sullivan; Feng Xu; William E Van Nostrand Journal: J Neuroinflammation Date: 2020-03-04 Impact factor: 9.587