Systemic inflammation driven by Aβ egress into the circulation via two-way transport systems such as the LDLR associated factors that circumvent the blood–brain barrier (BBB) [89,90] may contribute to AD progression by interfering with the clearance of Aβ by microglia, triggering tau hyperphosphorylation and the spread of NFT, as well as by promoting BBB breakdown [29,91,92,93,94]. This evidence concerns the gene LDLR and Alzheimer disease.