Back to Search
Start Over
BACE/APPV717F double-transgenic mice develop cerebral amyloidosis and inflammation.
- Source :
-
Neuro-degenerative diseases [Neurodegener Dis] 2005; Vol. 2 (6), pp. 284-98. - Publication Year :
- 2005
-
Abstract
- Most of the transgenic mice generated to model Alzheimer's disease express human amyloid precursor protein (APP) mutants alone or in conjunction with presenilin mutants. We have generated a mouse model by overexpressing human BACE and human APP with the V717F mutation. The combination of a mutation at the gamma-secretase cleavage site of APP and of increased beta-secretase activity should favour the production of amyloid peptides. We analysed double BACE/APPIn and single APPIn transgenic mice at 16-18 months for amyloid load, brain histopathology and behavioural deficits. We show that overexpression of BACE induces an increase in APP CTFbeta and total brain Abeta peptides. Brain histopathology shows clearly enhanced amyloid deposits in the cortex, hippocampus and in brain vasculature when compared to single APPIn transgenic mice. Amyloid deposits are mostly diffuse and predominantly composed of Abeta(42). A strong inflammatory reaction is evidenced by the presence of microglial cells around the most mature amyloid deposits and astrocytosis over the entire cerebral cortex. At the same age, the APPIn single-transgenic mice show only very limited pathology. When assessed for their cognitive performance at 12 months, BACE/APPIn mice show impaired spatial acquisition in the Morris water maze test. However, these deficits are not greater than those observed in the APPIn single-transgenic animals.
- Subjects :
- Amyloid Precursor Protein Secretases
Amyloid beta-Peptides metabolism
Amyloidosis psychology
Animals
Aspartic Acid Endopeptidases
Behavior, Animal physiology
Blotting, Western
Body Weight physiology
Encephalitis psychology
Enzyme-Linked Immunosorbent Assay
Genotype
Humans
Immunohistochemistry
In Situ Hybridization
Maze Learning physiology
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Mice, Transgenic
Motor Activity physiology
Mutation genetics
Peptide Fragments metabolism
Amyloid beta-Protein Precursor genetics
Amyloidosis genetics
Amyloidosis pathology
Encephalitis genetics
Encephalitis pathology
Endopeptidases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1660-2854
- Volume :
- 2
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Neuro-degenerative diseases
- Publication Type :
- Academic Journal
- Accession number :
- 16909011
- Full Text :
- https://doi.org/10.1159/000092314