INDUCED EXPRESSION OF NEURONAL MEMBRANE ATTACK COMPLEX AND CELL-DEATHBY ALZHEIMERS BETA-AMYLOID PEPTIDE

beta-amyloid peptide (A beta) and complement-derived membrane attack c omplex (MAC) are co-localized in senile plaques of brains from Alzheim er's disease (AD) patients. But the relationship between A beta and co mplement activation is unclear. We have used human neurotypic cells, d ifferentiated SH-SY5Y, as a model system to examine regulation of neur onal MAC expression and cell death by A beta. We demonstrated that mRN As (C1q, C2, C3, C4, C5, C6, C7, C8 and C9) and proteins (C1q, C3 and C9) for the major components of the classical complement cascade are p resent in the SH-SY5Y neurotypic cells, indicating that neuronal cells can synthesize the necessary proteins required for MAC formation. Fur thermore, immunocytochemical studies showed the A beta-induced neurona l MAC expression on the SH-SY5Y cells after CD59 was removed by PIPLC or blocked by anti-CD59 antibody. Meanwhile, increased A beta-induced neuronal cell death was observed following treatment with anti-CD59. T aken together, these results suggest that A beta activates neuronal co mplement cascade to induce MAC, and a deficiency of endogenous complem ent regulatory proteins, e.g., CD59, may increase the vulnerability of neurons to complement-mediated cytotoxicity. (C) 1998 Elsevier Scienc e B.V. All rights reserved.