Work

The App NL-G-F mouse model of Alzheimer’s disease is refractory to regulatory T cell treatment

Year: 2022

Type: preprint

Abstract: Background Alzheimer’s Disease is a neurodegenerative disease with a neuroinflammatory component. Due to the multifunctional capacity of regulatory T cells to prevent and reverse inflammation, regulatory T cells have been proposed as a potential therapeutic in Alzheimer’s Disease, either as a direct cell therapy or through the use of IL2 as a biologic to expand the endogenous population. Methods Here we characterize the longitudinal immunological changes occurring in T cells in the App NL-G-F mouse model of Alzheimer’s disease. Results Age-dependent immunological changes, in both the brain and periphery, occurred in parallel in both App NL-G-F mice and control App NL mice. As the endogenous IL2 axis was disturbed with age, we sought to determine the effect of IL2 supplementation on disease progression. Using a genetic model of IL2 provision in the periphery or in the brain, we found that expanding regulatory T cells in either location was unable to alter the progression of key pathological events or behavioral changes. Conclusion These results suggest that either the App NL-G-F mouse model does not recapitulate key regulatory T cell-dependent process of Alzheimer’s disease, or that regulatory T cell therapy is not a promising candidate for APP-mutation-driven Alzheimer’s disease.

Source: bioRxiv (Cold Spring Harbor Laboratory)

DOI: 10.1101/2022.03.11.483903