Characterization of the association of phospholipase C-delta with Alzheimer neurofibrillary tangles.
Phosphoinositide-specific phospholipase C (PLC) is a key enzyme in signal 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) 737-742]. To clarify the crucial involvement of abnormal PLC-delta accumulation contributing to the formation of NFT, we performed light and electron microscopic immunocytochemistry. To determine PLC-delta's association with NFT, its resistance to solubilization was also studied. Anti-PLC-delta antibody marked the same NFT-bearing neurons containing tau immunoreactivity with tau more clearly on NFT filaments and PLC-delta covering it superficially at the light microscope level. The double stained preparations with anti-PLC-delta antibody and bFGF binding suggested that PLC-delta 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-delta reacts mostly with amorphous granular materials, and occasionally with some abnormal filaments within NFT. Nevertheless, PLC-delta 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-delta are mainly present intraneuronally on the amorphous granular components of NFT as well as the abnormal filaments, suggesting PLC-delta's interactions and possible role in the formation of intraneuronal filamentous inclusions in AD.
Shimohama
S
S
Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
Perry
G
G
Richey
P
P
Praprotnik
D
D
Takenawa
T
T
Fukami
K
K
Whitehouse
P J
PJ
Kimura
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008854:Microscopy, Electron; D016874:Neurofibrillary Tangles / Q000201:enzymology* / Q000473:pathology; D013702:Temporal Lobe / Q000473:pathology; D010738:Type C Phospholipases / Q000032:analysis* / Q000276:immunology; D016875:tau Proteins / Q000276:immunology
D016875:tau Proteins; D010738:Type C Phospholipases