cAMP-induced decrease in cell-surface laminin receptor and cellular prion protein attenuates amyloid-beta uptake and amyloid-beta-induced neuronal cell death

Previous studies have shown that amyloid-beta oligomers (A beta O) bind with high affinity to cellular prion protein (PrPC). The A beta O-PrPC complex binds to cell-surface co-receptors, including the laminin receptor (67LR). Our current studies revealed that in Neuroscreen-1 cells, 67LR is the major co-receptor involved in the cellular uptake of A beta O and A beta Omicron-induced cell death. Both pharmacological (dibutyryl-cAMP, forskolin and rolipram) and physiological (pituitary adenylate cyclase-activating polypeptide) cAMP-elevating agents decreased cell-surface PrPC and 67LR, thereby attenuating the uptake of A beta O and the resultant neuronal cell death. These cAMP protective effects are dependent on protein kinase A, but not dependent on the exchange protein directly activated by cAMP. Conceivably, cAMP protects neuronal cells from A beta O-induced cytotoxicity by decreasing cell-surface-associated PrPC and 67LR.