In vivo infection models show that elevated TNF drives brain pathology in a Drosophila model of enterobacteria infection-aggravated AD.119 In mice, blocking TNF uptake at the BBB by inhibiting TNF receptor 1 (TNFR1) can reduce immune cell infiltration and ameliorate disease severity in a model of MS.120 Metabolite-immune cell interactions, intestinal barrier dysfunction, and bacterial infection can therefore be important early events in initiating neurodegenerative disease by altering gut-to-brain cytokine signaling and immune cell trafficking. This evidence concerns the gene TNF and neurodegenerative disease.