reMYND’s APP[V717I] x PS1[A246E] model

Complementary to the late onset APP-Ld single transgenics, an APP[V717I]xPS1[A246E] bigenic model has been developed being a more aggressive model with accelerated amyloid pathology [1]. These mice carry additionally the human PS1[A246E] transgene, also under control of the murine thy1 gene promoter, containing a clinical mutation in the transmembrane region.

The table below summarizes the key characteristics of reMYND’s proprietary APP[V717I]xPS1[A246E] Alzheimer transgenic mice, recapitulating important pathological and clinical hallmarks of Alzheimer’s disease and therefore valuable paradigms for evaluating therapeutic candidates.

reMYND's APPxPS1 model


Key Characteristics

APP[V717I] x

  • Expression of hAPP and hPS1 under control of moThy-1 gene promoter
  • More aggressive AD phenotype
    • Early-age amyloid plaque development (hippocampus, subiculum and cortex; as of 4.5 months)
    • Cognitive impairment; deficit in spatial reference memory (MWM) testing
    • Early Aβ-induced GSK3-activation and TAU phos phorylation in hippocampus
    • CAA pathology (as of 8 months)
    • Dystrophic neurites containing hyperphosphorylated moTau (no tangle-pathology)
    • Micro-bleedings (as of 12-15 months)
Dewachter et al., J. Neurosci., 2000

Complementary to the early onset APPxPS1 double transgenic, an APP[V717I] single transgenic model is available, featuring the main hallmarks but less aggressive.

A review paper, entitled ‘Pathological hallmarks, clinical parallels and value for drug testing in Alzheimer's disease of the APP[V717I] London transgenic mouse model’ reviews all key early and late hallmarks of the Alzheimer pathology in this model, and discusses clinical parallels with AD patients and the value of the APP-London transgenic mouse model for preclinical in vivo testing of experimental Alzheimer therapies. The paper also touches on reMYND’s other proprietary mouse models and is freely downloadable here.

For more information, please contact Bart Roucourt, CRO Manager.

[1] Dewachter I, Van Dorpe J, Smeijers L, Gilis M, Kuipéri C, Laenen I, Caluwaerts N, Moechars D, Checler F, Vanderstichele H, Van Leuven F. Aging increased amyloid peptide and caused amyloid plaques in brain of old APP/V717I transgenic mice by a different mechanism than mutant presenilin1. J. Neurosci. 20:6452-58 (2000).