Overview

Tg2576 mice overexpress a mutant form of amyloid precursor protein (APP), APPK670/671L, linked to early-onset familial Alzheimer’s disease (AD), developing amyloid plaques and progressive cognitive deficits. The Charles River AD platform with the Tg2576 mouse includes cognitive testing, measurement of the levels of soluble and insoluble beta amyloid, and immunohistochemical measurements. All studies can be customized according to client needs.

The Tg2576 mouse shows impaired cognitive functions in the contextual fear conditioning test, coinciding with the increased cortical and hippocampal soluble beta amyloid levels, starting from 5 months of age. The increased insoluble beta amyloid levels and the amyloid plaques are evident at 13 months of age.

Behavioral and Cognitive Tests

Motor Functions: Open Field Test

  • Total distance traveled
  • Distance traveled in the center area
  • Total rearing frequency
  • Rearing rate in the center area
  • Average velocity
  • Multiple other variables

Cognitive Deficits: Contextual Fear Conditioning Test (CFC)

  • Memory for context
  • Memory for cue
Testing/Validation Data
  • AMYLOID BETA ELISA

    Measurements of Beta Amyloid (Aβ) Levels:

    • 5 months of age
      • soluble Aβ1-40 and 1-42 from cortex and hippocampus
      • soluble Aβ1-42 from plasma and cerebrospinal fluid (CSF)
    • 13 months of age
      • soluble and insoluble Aβ1-40 and 1-42 from cortex and hippocampus
      • soluble Aβ1-40 and 1-42 from plasma and CSF
      • plaque load in cortex and hippocampus 
  • IMMUNOHISTOCHEMISTRY

    Immunohistochemistry and Other Measurements:

    • Astro- and microgliosis by GFAP and ED-1 IHC
    • Cytokine expression by IHC and/or ELISA (IL-1beta, IL-6)
    • Cell proliferation (neurogenesis) by BrdU and IHC with stereology (MAP-2, GFAP)
    • IDE activity assay
    • Phospho-GSK-3beta assay
    • Synaptophysin western blot
    • C99, C83 and holoAPP western blot
    • Neurochemical profile by anesthetized/awake microdialysis (ACh, 5HT, NE, DA, Glu, metabolites)
    • Plasma, cerebral tissue and microdialysate samples for PK and/or neurochemicals