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Meet the Switching Mice: They Flip Their Glia APOE4 to APOE2
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New Generation of Mouse Models Better Mimics Tauopathy, Alzheimer's
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06 Feb 2021
A new APP knock-in mouse has hit the scene. Researchers led by Pascal Sanchez, Denali Therapeutics, San Francisco, California, described the details in a paper posted to bioRxiv on January 20. They humanized the Aβ sequence in the mouse APP gene and knocked in three familial Alzheimer’s disease mutations: Swedish, Arctic, and Austrian. TREM2 expression and cytokine concentrations spiked in brain tissue, microglia flocked to plaques, neurites swelled, and tau and neurofilament light collected in their cerebrospinal fluid. Notably, microglia surrounding plaques seemed distressed the cells filled with lipids and revved up transcription of genes previously linked to a subset of microglia isolated from AD brain tissue. Denali, in collaboration with the Jackson Laboratory, will make this model open access for academics and companies alike.