ArticlebioRxiv : the preprint server for biology2026
5xFAD-NSG mice: a preclinical Alzheimer model for human cell therapy studies.
Article in bioRxiv : the preprint server for biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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4 authors.
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Abstract
Cellular therapies are one class of medicine being developed to treat Alzheimer's disease (AD), a neurodegenerative disease with memory loss, aberrant protein accumulation in the brain, and neuroinflammation. One challenge for development of human cell therapeutics is to have preclinical animal models that allow the use of human cells without immune-mediated rejection of those cells. The 5xFAD transgenic mouse model is a robust disease model for AD that expresses human amyloid precursor protein and presenilin-1 with multiple familial AD mutations, develops microglia-mediated neuroinflammation, accumulates amyloid-beta (Aβ) in the brain, and shows behavior changes with age. To create a mouse model for AD that permits the transplantation of human cells without immune-mediated rejection, we bred the 5xFAD transgenes onto the NOD-SCID-IL-2Rγ-deficient (NSG) mouse model to create 5xFAD-NSG mice. We report that 5xFAD-NSG mice develop Aβ plaques in the brain, microgliosis, neuroinflammation, and behavior changes that increase with age. We demonstrate that injection of CAR engineered human T regulatory cells are detected in the cerebral cortex and spleen after eight days. This 5xFAD-NSG mouse model for AD will be helpful to develop human cell-based therapies for AD.
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