CLDN8 and Alzheimer disease: In view of age-dependent blood-brain barrier breakdown in the human hippocampus (Montagne et al., 2015) and decreased claudin-8 expression (a member of tight junction proteins in endothelial cells) in kindled rat hippocampal tissues (Lamas et al., 2002), kindling may enhance the interplay of compromised hippocampal blood-brain barrier and pro-inflammatory signals and facilitate AD prolongation in the aging mice.