In a recent study on an animal model of ALS, elevated neuronal TAR DNA-binding protein 43 (TDP-43) levels induced microglial and astrocytic activation in the cortex, and exerted abundant immunoglobulin G, CD3, and CD4+ T cell infiltration as well as endothelial and pericyte activation, suggesting increased permeability of the BBB, thus enhancing the vulnerability of the cortex to the systemic inflammatory response [40], which in turn can initiate multiple pathways of neurodegeneration. Here, CD4 is linked to amyotrophic lateral sclerosis.