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BACE/APPV717F double-transgenic mice develop cerebral amyloidosis and inflammation.
Neurodegener Dis. 2005; 2(6):284-98.ND

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.

Authors+Show Affiliations

CNS Research, F Hoffmann-La Roche Ltd, Basel, Switzerland. laurence.ozmen@roche.comNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16909011

Citation

Ozmen, Laurence, et al. "BACE/APPV717F Double-transgenic Mice Develop Cerebral Amyloidosis and Inflammation." Neuro-degenerative Diseases, vol. 2, no. 6, 2005, pp. 284-98.
Ozmen L, Woolley M, Albientz A, et al. BACE/APPV717F double-transgenic mice develop cerebral amyloidosis and inflammation. Neurodegener Dis. 2005;2(6):284-98.
Ozmen, L., Woolley, M., Albientz, A., Miss, M. T., Nelboeck, P., Malherbe, P., Czech, C., Gruninger-Leitch, F., Brockhaus, M., Ballard, T., & Jacobsen, H. (2005). BACE/APPV717F double-transgenic mice develop cerebral amyloidosis and inflammation. Neuro-degenerative Diseases, 2(6), 284-98.
Ozmen L, et al. BACE/APPV717F Double-transgenic Mice Develop Cerebral Amyloidosis and Inflammation. Neurodegener Dis. 2005;2(6):284-98. PubMed PMID: 16909011.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - BACE/APPV717F double-transgenic mice develop cerebral amyloidosis and inflammation. AU - Ozmen,Laurence, AU - Woolley,Marie, AU - Albientz,Anita, AU - Miss,Marie-Therese, AU - Nelboeck,Peter, AU - Malherbe,Pari, AU - Czech,Christian, AU - Gruninger-Leitch,Fiona, AU - Brockhaus,Manfred, AU - Ballard,Theresa, AU - Jacobsen,Helmut, PY - 2005/11/09/accepted PY - 2006/8/16/pubmed PY - 2006/10/5/medline PY - 2006/8/16/entrez SP - 284 EP - 98 JF - Neuro-degenerative diseases JO - Neurodegener Dis VL - 2 IS - 6 N2 - 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. SN - 1660-2854 UR - https://www.unboundmedicine.com/medline/citation/16909011/BACE/APPV717F_double_transgenic_mice_develop_cerebral_amyloidosis_and_inflammation_ L2 - https://www.karger.com?DOI=10.1159/000092314 DB - PRIME DP - Unbound Medicine ER -