Genetic, Transcriptome, Proteomic, and Epidemiological Evidence for Blood-Brain Barrier Disruption and Polymicrobial Brain Invasion as Determinant Factors in Alzheimer’s Disease

Carter, Chris J.

It has also been noted that unaffected offspring with a parental history of AD have an enhanced inflammatory response in LPS-stimulated whole blood samples, producing higher levels of interleukin 1 beta, tumor necrosis factor alpha, and interferon gamma in response to LPS. This effect was independent of the APOE4 variant [138] suggesting that other AD genes are also endowed with gain of function in relation to the immune/inflammatory system. Monocyte-derived dendritic cells from AD patients also produce more interleukin-6 than those from healthy controls. AD monocytes stimulated with LPS also show a higher induced expression of the pro-inflammatory ICAM1 adhesion molecule than controls [139] . A␤ also stimulates cytokine production in peripheral blood mononuclear cells (PBMC) and the production of the chemokines, RANTES, MIP-1beta, and eotaxin as well as that of CSF2 (colony stimulating factor 2 (granulocyte-macrophage)) and CSF3 (colony stimulating factor 3) is greater than controls in AD-derived PBMC stimulated with A␤ [140] .