Some studies indicate reduction in tight junction proteins (ZO-1, occluding, and claudin-5) before motor neuron loss, in presymptomatic ALS stages [188], while other data point out the reduction in tight junctions proteins (ZO-1 and occludin) and basement membrane protein agrin in symptomatic ALS stages [187]. Here, CLDN5 is linked to amyotrophic lateral sclerosis.