title: Characterization of the brain β-amyloid isoform pattern at different ages of Tg2576 mice.
abstract: BACKGROUND
  Although genetic and biochemical studies have suggested a cardinal role for β-amyloid (Aβ) in Alzheimer's disease, the underlying mechanism(s) of how Aβ induces neurodegeneration is still unclear. Our objective was to investigate the consequences of Aβ, 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 Aβ isoform pattern. Young animals displayed high cortical levels of the shorter Aβ isoforms (Aβ1-16 and Aβ1-17) compared to 15-month-old Tg2576 mice which mainly expressed Aβ1-40 and Aβ1-42. The Aβ1-42 showed an age-dependent increase, whereas total Aβ1-40 levels remained constant. The highest levels of TBS-soluble Aβ oligomers were found at 90 days of age. Brain Aβ build-up did not affect the phosphorylation of tau at the epitopes investigated.
  
  
  CONCLUSIONS
  This study provides new information about age-dependent Aβ 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 Aβ isoforms do not directly cause increased tau phosphorylation and that the cognitive deficits seen in this mouse model are only related to the Aβ overexpression.
authors.affiliation: Division of Alzheimer Neurobiology, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden.
authors.forename: Tamanna
authors.initials: T
authors.lastname: Mustafiz
authors.forename: Erik
authors.initials: E
authors.lastname: Portelius
authors.forename: Mikael K
authors.initials: MK
authors.lastname: Gustavsson
authors.forename: Mikko
authors.initials: M
authors.lastname: Hölttä
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Agneta
authors.initials: A
authors.lastname: Nordberg
authors.forename: Christina Unger
authors.initials: CU
authors.lastname: Lithner
mesh_terms: D000375:Aging / Q000473:pathology* / Q000502:physiology*; D016229:Amyloid beta-Peptides / Q000096:biosynthesis / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000473:pathology / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology; D002540:Cerebral Cortex / Q000473:pathology* / Q000502:physiology*; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020033:Protein Isoforms / Q000096:biosynthesis / Q000737:chemistry*; D011498:Protein Precursors / Q000096:biosynthesis / Q000737:chemistry
chemical_list: D016229:Amyloid beta-Peptides; D020033:Protein Isoforms; D011498:Protein Precursors