Harmony of T cell profile in brain, nasal, spleen, and cervical lymph nodes tissues in Alzheimer’s: A systemic disease with local manifestations

The brain has special importance and is known as immune privileged site to and from which trafficking of immune cells is tightly regulated. However, in Alzheimer's disease (AD) the balance of the immune system is disturbed and damages the brain. Given the anatomical and immunological barriers in the brain, we attempted to evaluate if the neuroinflammation occurred in AD is limited to the brain or is expanded to the periphery. Hence, rat model of AD was induced by intra-hippocampal injection of beta-amyloid1-42. Then, nasal, brain, cervical lymph nodes, and spleen were isolated. Then, profile of T-helper (Th)1, Th2, and Th17, represented by IFN-γ, IL-4, and IL-17, respectively, was determined. The results were compared between the organs and with the corresponding tissue in normal animals. IFN-γ and IL-17 levels in the brain, nasal tissue, and cervical lymph nodes of AD model were higher than IL-4, comparing with normal animals. Similar profile was observed in the spleen. The results suggest Alzheimer's as a systemic disease whose complication are observed locally. The possibility of epitope spreading and autoimmune nature of AD is raised again. Interestingly, although AD model was induced by injection of beta-amyloid in the brain, the cellular responses in the brain and nasal tissue were similar indicating that the nasal-brain axis is two-sided. In addition, both of IFN-γ/IL-17 and IL-4/IL-17 ratios, just in nasal tissue were markedly decreased in AD model comparing with normal animals. This suggests development of future nasal-based diagnostic approaches.