CLDN5 and amyotrophic lateral sclerosis: BCSFB alterations are also present in diseases such as amyotrophic lateral sclerosis (ALS) in which patients display elevated total protein levels and increased blood proteins in the CSF, indicating that there may be disruption of the barrier and/or decreased clearing, which was also confirmed by transcriptomic and immunohistochemistry studies where the expression and patterns of claudin-5 and zonula occludens-1, respectively, were downregulated [31].