Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
| Autor: | Thomas Donaldson, J. C. Clemens, Michael Power, Dale Schenk, Michael K. Lee, Robin Barbour, Lisa McConlogue, Frances Gillespie, James Vitale, Ferdie Soriano, Eliezer Masliah, Karen Khan, Lennart Mucke, Dora Games, Sam Wadsworth, Patricia Borthelette, Ree Alessandrini, Sheila P. Little, Jun Zhao, Ivan Lieberburg, Hua Tan, Elizabeth Penniman, Paul Leibowitz, Tony Carr, Peter Seubert, Stephanie Hagopian, Martin Montoya-Zavala, Ben Wolozin, Kelly Johnson-Wood, Ben W. Snyder, Catherine Blackwell, Terry Guido, Lisa Paganini, David S. Adams |
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| Rok vydání: | 1995 |
| Předmět: |
Amyloid
Molecular Sequence Data BACE1-AS Mice Transgenic Immunoenzyme Techniques Amyloid beta-Protein Precursor Mice chemistry.chemical_compound Alzheimer Disease mental disorders Amyloid precursor protein medicine Animals Humans Senile plaques DNA Primers Platelet-Derived Growth Factor Amyloid beta-Peptides Microscopy Confocal Multidisciplinary Base Sequence biology P3 peptide Brain medicine.disease Biochemistry of Alzheimer's disease Cell biology chemistry Mutation biology.protein Thioflavin Alzheimer's disease |
| Zdroj: | Nature. 373:523-527 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/373523a0 |
| Popis: | Alzheimer's disease (AD) is the most common cause of progressive intellectual failure in aged humans. AD brains contain numerous amyloid plaques surrounded by dystrophic neurites, and show profound synaptic loss, neurofibrillary tangle formation and gliosis. The amyloid plaques are composed of amyloid beta-peptide (A beta), a 40-42-amino-acid fragment of the beta-amyloid precursor protein (APP). A primary pathogenic role for APP/A beta is suggested by missense mutations in APP that are tightly linked to autosomal dominant forms of AD. A major obstacle to elucidating and treating AD has been the lack of an animal model. Animals transgenic for APP have previously failed to show extensive AD-type neuropathology, but we now report the production of transgenic mice that express high levels of human mutant APP (with valine at residue 717 substituted by phenylalanine) and which progressively develop many of the pathological hallmarks of AD, including numerous extracellular thioflavin S-positive A beta deposits, neuritic plaques, synaptic loss, astrocytosis and microgliosis. These mice support a primary role for APP/A beta in the genesis of AD and could provide a preclinical model for testing therapeutic drugs. |
| Databáze: | OpenAIRE |
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