Characterization of the Brain β-Amyloid Isoform Pattern at Different Ages of Tg2576 Mice

Background: Although genetic and biochemical studies have suggested a cardinal role for beta-amyloid (A beta) in Alzheimer's disease, the underlying mechanism(s) of how A beta induces neurodegeneration is still unclear. Our objective was to investigate the consequences of A beta, 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 beta isoform pattern. Young animals displayed high cortical levels of the shorter A beta isoforms (A beta 1-16 and A beta 1-17) compared to 15-month-old Tg2576 mice which mainly expressed A beta 1-40 and A beta 1-42. The A beta 1-42 showed an age-dependent increase, whereas total A beta 1-40 levels remained constant. The highest levels of TBS-soluble A beta oligomers were found at 90 days of age. Brain A beta build-up did not affect the phosphorylation of tau at the epitopes investigated. Conclusions: This study provides new information about age-dependent A beta 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 beta isoforms do not directly cause increased tau phosphorylation and that the cognitive deficits seen in this mouse model are only related to the A beta overexpression. Copyright (C) 2011 S. Karger AG, Basel