Epitopes described in "Characterization of the brain β-amyloid isoform pattern at different ages of Tg2576 mice."

Article Authors:Tamanna Mustafiz; Erik Portelius; Mikael K Gustavsson; Mikko Hölttä; Henrik Zetterberg; Kaj Blennow; Agneta Nordberg; Christina Unger Lithner
Article Title:Characterization of the brain β-amyloid isoform pattern at different ages of Tg2576 mice.
Reference Detail
Reference ID:1021987
Abstract:BACKGROUND: Although genetic and biochemical studies have suggested a cardinal role for -amyloid (A) in Alzheimer's disease, the underlying mechanism(s) of how A induces neurodegeneration is still unclear. Our objective was to investigate the consequences of A, especially on tau phosphorylation at specific epitopes important for Alzheimer's disease. METHODS: We used cortices from Tg2576 mice at 7 days to 15 months of age. RESULTS: MALDI-TOF MS revealed an age-dependent shift in the A isoform pattern. Young animals displayed high cortical levels of the shorter A isoforms (A1-16 and A1-17) compared to 15-month-old Tg2576 mice which mainly expressed A1-40 and A1-42. The A1-42 showed an age-dependent increase, whereas total A1-40 levels remained constant. The highest levels of TBS-soluble A oligomers were found at 90 days of age. Brain A build-up did not affect the phosphorylation of tau at the epitopes investigated. CONCLUSIONS: This study provides new information about age-dependent A isoforms and oligomers as well as their effect on site-specific tau phosphorylation in this transgenic mouse model. Our observations suggest that the different human A isoforms do not directly cause increased tau phosphorylation and that the cognitive deficits seen in this mouse model are only related to the A overexpression.
Affiliations:Division of Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
Reference Type:Literature
PubMed ID:21346320
Journal:Neurodegener Dis
Journal Volume:8
Article Pages:352-63
Journal ISSN:1660-2854
Article Chemical List:Amyloid beta-Peptides;Protein Isoforms;Protein Precursors
Article MeSH List:Aging(pathology; physiology); Amyloid beta-Peptides(biosynthesis; chemistry); Animals; Brain(pathology; physiology); Brain Chemistry(physiology); Cerebral Cortex(pathology; physiology); Male; Mice; Mice, Transgenic; Protein Isoforms(biosynthesis; chemistry); Protein Precursors(biosynthesis; chemistry)
Curation Last Updated:2014-10-03 22:20:22