Discussion
Our data contribute additional mechanistic insight into the detrimental role of the MR1/MAIT cell axis in AD pathology development. Highlights: 5XFAD mice lacking the innate immune MR1/MAIT (mucosal-associated invariant T) cell axis (5XFAD/MR1 KO) have reduced numbers of dystrophic neurite markers in the hippocampus at 8 months of age. Hippocampal tissue transcriptional analyses showed reduced expression of genes encoding classical dystrophic neurite markers in 5XFAD/MR1 KO mice. 5XFAD/MR1 KO mice had less insoluble amyloid beta 40 and increased levels of the post-synaptic marker, postsynaptic density protein 95, in the hippocampus than did MR1+ 5XFAD mice.
Methods
Brain tissue from 5XFAD mice and those that are MR1 deficient (MR1 KO), were analyzed for dystrophic neurites, amyloid plaques, and synapses via immunofluorescence, RNA sequencing, enzyme-linked immunosorbent assay, and western blot.
Results
In 8-month-old 5XFAD/MR1 KO mice, there was reduced expression of lysosomal-associated membrane protein 1, ubiquitin, and n-terminal amyloid precursor protein in the hippocampus compared to 5XFAD mice (P < 0.05). 5XFAD/MR1 KO mice also had less insoluble amyloid beta 40 (P < 0.001) and higher levels of postsynaptic density protein 95 (P < 0.01) in the hippocampus.