Abstract

The hypothesis that forms the basis of this proposal is that expression of human hereditary cerebral hemorrhage with amyloidosis Dutch-type (HCHWA-D) mutant amyloid beta-protein precursor (ABPP) in the smooth muscle cells of cerebral blood vessels of transgenic mice will lead to cerebral amyloid angiopathy (CAA). The applicants plan to create transgenic mice that will express human ABPP carrying the HCHWA-D mutation in vascular smooth muscle cells in order to test the above hypothesis. Once they obtain positive transgenic mice, they will conduct specific immunohistochemical staining and immunoblotting studies on brain and other tissues from the transgenic mice to quantitatively and qualitatively determine the extent and distribution of human wild-type or HCHWA-D mutant ABPP protein expression. In addition, they will perform Northern blot analyses. Lastly, they will examine the transgenic mice for key pathological signs that are characteristic of CAA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS036645-02
Application #
2892287
Study Section
Special Emphasis Panel (ZRG1-NLS-1 (02))
Program Officer
Murphy, Diane
Project Start
1998-05-01
Project End
2001-04-30
Budget Start
1999-05-01
Budget End
2000-04-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
State University New York Stony Brook
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794

  Publications

Xu, Feng; Vitek, Michael P; Colton, Carol A et al. (2012) Human apolipoprotein E2 promotes parenchymal amyloid deposition and neuronal loss in vasculotropic mutant amyloid-ýý protein Tg-SwDI mice. J Alzheimers Dis 31:359-69
Xu, Feng; Vitek, Michael P; Colton, Carol A et al. (2008) Human apolipoprotein E redistributes fibrillar amyloid deposition in Tg-SwDI mice. J Neurosci 28:5312-20
Vasilevko, Vitaly; Xu, Feng; Previti, Mary Lou et al. (2007) Experimental investigation of antibody-mediated clearance mechanisms of amyloid-beta in CNS of Tg-SwDI transgenic mice. J Neurosci 27:13376-83
Xu, F; Grande, A M; Robinson, J K et al. (2007) Early-onset subicular microvascular amyloid and neuroinflammation correlate with behavioral deficits in vasculotropic mutant amyloid beta-protein precursor transgenic mice. Neuroscience 146:98-107
Fan, Rong; DeFilippis, Kelly; Van Nostrand, William E (2007) Induction of complement proteins in a mouse model for cerebral microvascular A beta deposition. J Neuroinflammation 4:22
Xu, Feng; Previti, Mary Lou; Van Nostrand, William E (2007) Increased severity of hemorrhage in transgenic mice expressing cerebral protease nexin-2/amyloid beta-protein precursor. Stroke 38:2598-601
Fan, Rong; Xu, Feng; Previti, Mary Lou et al. (2007) Minocycline reduces microglial activation and improves behavioral deficits in a transgenic model of cerebral microvascular amyloid. J Neurosci 27:3057-63
Carrasco, J; Adlard, P; Cotman, C et al. (2006) Metallothionein-I and -III expression in animal models of Alzheimer disease. Neuroscience 143:911-22
Herzig, Martin C; Van Nostrand, William E; Jucker, Mathias (2006) Mechanism of cerebral beta-amyloid angiopathy: murine and cellular models. Brain Pathol 16:40-54
Davis, Judianne; Xu, Feng; Miao, Jianting et al. (2006) Deficient cerebral clearance of vasculotropic mutant Dutch/Iowa Double A beta in human A betaPP transgenic mice. Neurobiol Aging 27:946-54

Showing the most recent 10 out of 17 publications