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- Many genetic risk factors interact with the lipoprotein related receptor protein, LRP. LRP appears to be the common link among multiple proteins relevant to AD. Three of the genes where mutations impart increased susceptibility to AD: APP,alpha 2 macroglobulin encode proteins that are ligands for LRP and even LRP itself may be a risk factor (C/C) allele. This may be in part via effects on oligomerization. The TGFß ligands particularly TGFß2, increase oligomerization, which increases the toxicity of amyloid. Evidence suggests that LRP affects the
processing of APP and amyloid ß protein production. LRP may have a double edged sword effect because on one had, LRP on vascular cells or ependyma, may help clear amyloid out of the brain, while LRP on neurons, may increase its uptake by neurons, killing the c ells, and perhaps explaining why LRP is lost early in the disease process. for more information on this topic see this paper.