Anti-LRP/LR specific antibody IgG1-iS18 and knock-down of LRP/LR by shRNAs rescue cells from Aβ(42) induced cytotoxicity

Alzheimer's disease (AD) is characterized by neurofibrillary tangles, senile plaques and neuronal loss. Amyloid beta (Aβ) is proposed to elicit neuronal loss through cell surface receptors. As Aβ shares common binding partners with the 37 kDa/67 kDa laminin receptor (LRP/LR), we investigated whether these proteins interact and the pathological significance of this association. An LRP/LR-Αβ(42) interaction was assessed by immunofluorescence microscopy and pull down assays. The cell biological effects were investigated by 3-(4,5-Dimethylthaizol-2-yl)-2,5-diphenyltetrazolium bromide and Bromodeoxyuridine assays. LRP/LR and Αβ(42) co-localised on the cell surface and formed immobilized complexes suggesting an interaction. Antibody blockade by IgG1-iS18 and shRNA mediated down regulation of LRP/LR significantly enhanced cell viability and proliferation in cells co-treated with Αβ(42) when compared to cells incubated with Αβ(42) only. Results suggest that LRP/LR is implicated in Αβ(42) mediated cytotoxicity and that anti-LRP/LR specific antibodies and shRNAs may serve as potential therapeutic tools for AD.