Analysis of N-cadherin interacting proteins in Alzheimer's diesase

In Alzheimer's disease, synaptic loss correlates with the severity of cognitive impairment. N-cadherin, a cell-adhesion molecule, is localized to synapses and regulates synaptic contact. Presenilin 1, whose mutations are linked to Familial Alzheimer's disease, associates N-cadherin at synapses and cleaves it as a component of gamma-secretase complex. But the mechanism of synaptic loss in Alzheimer's disease was not understood well, so we investigated N-cadherin interacting proteins which could distinguish Alzheimer's disease from the other diseases. We examined human brain samples by immunoprecipitation assay using anti-N-cadherin antibody followed by silver staining. Mass spectrometry identified a N-cadherin interacting protein. We confirmed this interaction in both murine primary neurons and HEK293 cells, and binding domain was identified by immunoprecipitation assay. This protein is involved with mitogen activated protein kinase (MAPK) signaling pathway, so we studied the effect of N-cadherin on that MAPK signaling pathway. We transfected the plasmid of N-cadherin into COS-7 cells, western blot analysis was performed. This experiment showed that overexpression of N-cadherin had negative effect on that MAPK signaling pathway. N-cadherin expression had a negative effect on MAPK signaling pathway. We investigated the role of this novel N-cadherin-MAPK signaling pathway in Alzheimer's disease.