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Peripheral adaptive immunity of the triple transgenic mouse model of Alzheimer's disease 11 Medical and Health Sciences 1107 Immunology

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Abstract

Background: Immunologic abnormalities have been described in peripheral blood and central nervous system of patients suffering from Alzheimer's disease (AD), yet their role in the pathogenesis still remains poorly defined. Aim and methods: We used the triple transgenic mouse model (3xTg-AD) to reproduce Aβ (amyloid plaques) and tau (neurofibrillary tangles) neuropathologies. We analyzed important features of the adaptive immune system in serum, primary (bone marrow) as well as secondary (spleen) lymphoid organs of 12-month-old 3xTg-AD mice using flow cytometry and ELISPOT. We further investigated serum cytokines of 9- A nd 13-month-old 3xTg-AD mice using multiplex ELISA. Results were compared to age-matched non-transgenic controls (NTg). Results: In the bone marrow of 12-month-old 3xTg-AD mice, we detected decreased proportions of short-term reconstituting hematopoietic stem cells (0.58-fold, P = 0.0116), while lymphocyte, granulocyte, and monocyte populations remained unchanged. Our results also point to increased activation of both B and T lymphocytes. Indeed, we report elevated levels of plasma cells in bone marrow (1.3-fold, P = 0.0405) along with a 5.4-fold rise in serum IgG concentration (P < 0.0001) in 3xTg-AD animals. Furthermore, higher levels of interleukin (IL)-2 were detected in serum of 9- A nd 13-month-old 3xTg-AD mice (P = 0.0018). Along with increased concentrations of IL-17 (P = 0.0115) and granulocyte-macrophage colony-stimulating factor (P = 0.0085), these data support helper T lymphocyte activation with Th17 polarization. Conclusion: Collectively, these results suggest that the 3xTg-AD model mimics modifications of the adaptive immunity changes previously observed in human AD patients and underscore the activation of both valuable and harmful pathways of immunity in AD.

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St-Amour, I., Bosoi, C. R., Paré, I., Ignatius Arokia Doss, P. M., Rangachari, M., Hébert, S. S., … Calon, F. (2019). Peripheral adaptive immunity of the triple transgenic mouse model of Alzheimer’s disease 11 Medical and Health Sciences 1107 Immunology. Journal of Neuroinflammation, 16(1). https://doi.org/10.1186/s12974-018-1380-5

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