First, blood–brain barrier permeability is increased in mouse models disrupted for glucocerebrosidase (Gbaflox/flox; nestin-Cre; modeling Gaucher disease), beta-hexosaminidase mice (modeling Sandhoff disease) or beta-galactosidase-1 (modeling GM1 gangliosidosis), as evidenced with gadolinium diethylenetriaminepentaacetic acid or Evans blue extravasation [121, 124]. Here, NES is linked to GM1 gangliosidosis.