| Autor: |
Stefano Suzzi, Tommaso Croese, Adi Ravid, Or Gold, Abbe R. Clark, Sedi Medina, Daniel Kitsberg, Miriam Adam, Katherine A. Vernon, Eva Kohnert, Inbar Shapira, Sergey Malitsky, Maxim Itkin, Sarah P. Colaiuta, Liora Cahalon, Michal Slyper, Anna Greka, Naomi Habib, Michal Schwartz |
| Rok vydání: |
2022 |
| Popis: |
Systemic immunity supports healthy brain homeostasis. Accordingly, conditions causing systemic immune deregulation may accelerate onset of neurodegeneration in predisposed individuals. Here we show that, in the 5xFAD mouse model of Alzheimer’s disease (AD), high-fat diet-induced obesity accelerated cognitive decline, which was associated with immune deviations comprising increased splenic frequencies of exhausted CD4+T effector memory cells and CD4+FOXP3+regulatory T cells (Tregs). Non-targeted plasma metabolomics identifiedN-acetylneuraminic acid (NANA), the predominant sialic acid, as the major obesity-induced metabolite in 5xFAD mice, the levels of which directly correlated with Tregs abundance and inversely correlated with cognitive performance. Visceral adipose tissue macrophages were identified by sNuc-Seq as one potential source of NANA. Exposure to NANA led to immune deregulation in middle-aged wild-type mice, andex vivoin human T cells. Our study identified diet-induced immune deregulation, potentially via sialic acid, as a previously unrecognized link between obesity and AD. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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