Thy1-ApoE4/C/EBPβ double transgenic mice act as a sporadic model with Alzheimer's disease

Early onset familial Alzheimer's disease (FAD) with APP, PS1/2 (presenilins) mutation accounts for only a small portion of AD cases, and most are late-onset sporadic. However, majority of AD mouse models are developed to mimic the genetic cause of human AD by overexpressing mutated forms of human APP, PS1/2, and/or Tau protein, though there is no Tau mutation in AD, and no single mouse model recapitulates all aspects of AD pathology. Here, we report Thy1-ApoE4/C/EBP beta double transgenic mouse model that demonstrates key AD pathologies in an age-dependent manner in absence of any human APP or PS1/2 mutation. Using the clinical diagnosis criteria, we show that this mouse model exhibits tempo-spatial features in AD patient brains, including progressive cognitive decline associated with brain atrophy, which is accompanied with extensive neuronal degeneration. Remarkably, the mice display gradual A beta aggregation and neurofibrillary tangles formation in the brain validated by A beta PET and Tau PET. Moreover, the mice reveal widespread neuroinflammation as shown in AD brains. Hence, Thy1-ApoE4/C/EBP beta mouse model acts as a sporadic AD mouse model, reconstituting the major AD pathologies.