CHARACTERIZATION OF THE ASSOCIATION OF PHOSPHOLIPASE C-DELTA WITH ALZHEIMER NEUROFIBRILLARY TANGLES

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in sig nal transduction. We have previously demonstrated that an antibody to the PLC isozyme, PLC-delta, intensely stained neurofibrillary tangles (NFT) in the brain tissue of AD patients [Am. J. Pathol, 139 (1991) 73 7-742]. To clarify the crucial involvement of abnormal PLC-delta accum ulation contributing to the formation of NFT, we performed light and e lectron microscopic immunocytochemistry. To determine PLC-delta's asso ciation with NFT, its resistance to solubilization was also studied. A nti-PLC-delta antibody marked the same NFT-bearing neurons containing tau immunoreactivity with tau more clearly on NFT filaments and PLC-de lta covering it superficially at the light microscope level. The doubl e stained preparations with anti-PLC-delta antibody and bFGF binding s uggested that PLC-delta is an intracellular marker and is not retained after neuronal death. Employing immunoperoxidase and immunogold elect ron microscopic immunocytochemistry, we found that the antibody to PLC -delta reacts mostly with amorphous granular materials, and occasional ly with some abnormal filaments within NFT. Nevertheless, PLC-delta in NFT was resistant to removal by high salt or ionic detergent, indicat ing it is an integral NFT component. These results indicate that antig enic determinants unique to PLC-delta are mainly present intraneuronal ly on the amorphous granular components of NFT as well as the abnormal filaments, suggesting PLC-delta's interactions and possible role in t he formation of intraneuronal filamentous inclusions in AD.