In the AxD models examined: Gfap+/R236H mutant, GFAP over-expressing transgenic (GFAPTg), and double Gfap+/R236H/GFAPTg mice, with increasing severity respectively, loss of Nrf2 does not worsen the apparent phenotype, including life-span, body weight or the distribution of Rosenthal fibers in the brain. Here, NFE2L2 is linked to Alexander disease.