Combining our data with those of the literature, we suggest the following, more or less chronological order of events taking place at the CPE in AD: increased amyloid burden on CPE; increased oxidative stress; despite continuous and high TTR production: decrease of CPE capability to handle increased amyloid burden; (pro-) inflammatory signalling; intracellular ubiquitin involvement; remodelling of adherens and tight junctions (CLDN5) causing increased permeability, and, finally, cellular atrophy and barrier disintegration. This evidence concerns the gene CLDN5 and Alzheimer disease.