An App knock-in rat model for Alzheimer’s disease exhibiting Aβ and tau pathologies, neuronal death and cognitive impairments
抄録
<jats:title>Abstract</jats:title><jats:p>A major obstacle in Alzheimer’s disease (AD) research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy. Transgenic mice overexpressing amyloid precursor protein (<jats:italic>App</jats:italic>) gene manifest non-physiological and ectopic expression of APP and its fragments in the brain, which is not observed in AD patients. The<jats:italic>App</jats:italic>knock-in mice circumvented some of these problems, but they do not exhibit tau pathology and neuronal death. We have generated a rat model, with three familiar<jats:italic>App</jats:italic>mutations and humanized Aβ sequence knocked into the rat<jats:italic>App</jats:italic>gene. Without altering the levels of full-length APP and other APP fragments, this model exhibits pathologies and disease progression resembling those in human patients: deposit of Aβ plaques in relevant brain regions, microglia activation and gliosis, progressive synaptic degeneration and AD-relevant cognitive deficits. Interestingly, we have observed tau pathology, neuronal apoptosis and necroptosis and brain atrophy, phenotypes rarely seen in other APP models. This<jats:italic>App</jats:italic>knock-in rat model may serve as a useful tool for AD research, identifying new drug targets and biomarkers, and testing therapeutics.</jats:p>
収録刊行物
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- Cell Research
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Cell Research 32 (2), 157-175, 2021-11-17
Springer Science and Business Media LLC