Intriguingly, polymorphisms in the gene encoding the backup acetyl choline hydrolyzing enzyme butyrylcholinesterase are reported as risk factors in both ATH and AD. Choles inhibitor bulk terol hemisuccinate is a weak inhibitor of BChE but a potent inhibitor of AChE. AChE inhibitors may therefore act, in part, via interference with steroid and sterol metabolism. AChE is widely expressed at the surface of platelets and red blood cells, macrophages express specific nico tinic acetyl choline receptors, and systemic cholinergic Inhibitors,Modulators,Libraries signaling Inhibitors,Modulators,Libraries modulates platelet aggregation, macrophage function, and innate immunity. Interaction with these pathways, either directly or via CNS effects, could underlie the beneficial effects of AChE inhibition in both ATH and AD.

The overlaps in drug responsiveness between AD and ATH reinforce Rohers earlier observation that there is an immediate need for prospective clinical Inhibitors,Modulators,Libraries trials to as sess the efficacy of AD prevention using antiathero sclerotic agents. Equally do other anti AD drugs combat ATH Transcriptome module overlap Inhibitors,Modulators,Libraries Further evidence of commonality between AD and ATH is provided by gene expression Inhibitors,Modulators,Libraries analysis. Ray et al. used a systems biology approach to analyze brain RNAs from 20 confirmed AD brains versus 13 controls. 1600 genes differentially expressed in AD were identified and classified according to functional module. The two pre dominant modules, confirmed by functional annotation clustering, were AD neurodegeneration, as expected, but also cardiovascular coronary artery disease.

The authors concluded that many pathways are common to both diseases, their results provide strong support for a mechanistic linkage EPZ-5676 Histone Methyltransferase inhibitor between AD and ATH. Mechanisms inflammation, cholesterol metabolism, immunosterols Both diseases are underpinned by genes affecting choles terol transport metabolism and immunity. Immunosti mulation precipitated by infectious agents or specific components such as LPS can increase, sometimes dra matically, the development of ATH or AD in animal models. Equally compelling are the data that the im mune system, notably macrophages, is centrally involved in the disease processes that culminate in local inflam mation, the formation of cholesterol loaded foam cells, and vascular occlusion. These observations point to a direct link between infection and cholesterol metabol ism, as borne out by studies on APOE. APOE and infection APOE alleles, encoding a key lipid transport molecule, play a crucial determining role in the outcome of viral and bacterial infection. In mouse models, APOE modu lates infection by HSV 1, Chlamydophila, Klebsiella pneumoniae, Listeria monocytogenes and Leishmania.