Characterization of the association of phospholipase C-δ with Alzheimer neurofibrillary tangles

Abstract

Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal transduction. We have previously demonstrated that an antibody to the PLC isozyme, PLC-δ, intensely stained neurofibrillary tangles (NFT) in the brain tissue of AD patients [ Am. J. Pathol., 139 (1991) 737–742]. To clarify the crucial involvement of abnormal PLC-δ accumulation contributing to the formation of NFT, we performed light and electron microscopic immunocytochemistry. To determine PLC-δ's association with NFT, its resistance to solubilization was also studied. Anti-PLC-δ antibody marked the same NFT-bearing neurons containing τ immunoreactivity with τ more clearly on NFT filaments and PLC-δ covering it superficially at the light microscope level. The double stained preparation with anti-PLC-δ antibody and bFGF binding suggested that PLC-δ is an intracellular marker and is not retained after neuronal death. Employing immunoperoxidase and immunogold electron microscopic immunocytochemistry, we found that the antibody to PLC-δ reacts mostly with amorphous granular materials, and occasionally with some abnormal filaments within NFT. Nevertheless, PLC-δ in NFT was resistant to removal by high salt or ionic detergent, indicating it is an integral NFT component. These results indicate that antigenic determinants unique to PLC-δ are mainly present intraneuronally on the amorphous granular components of NFT as well as the abnormal filaments, suggesting PLC-δ's interactions and possible role in the formation of intraneuronal filamentous inclusions in AD.