IL1B and Alzheimer disease: Proinflammatory cytokines TNF-α and IL1-β activate the canonical NF-κB pathway that induce the gene expression of cyclooxigenase-2, inducible nitric oxide synthase-3, inflammatory cytokines, and matrix metalloproteinases [75] These changes lead to the damage of TJs, decreased endothelial integrity and increased permeability at the BBB [73, 76], and to neuroinflammation and the development of chronic neurodegenerative diseases such as AD [10, 77].