Aberrant accumulation of phospholipase C-delta in Alzheimer brains

Since phosphoinositide-specific phospholipase C (PLC) is one of the key molecules in signal transduction, the authors assessed its involvement in Alzheimer's disease (AD). Immunostaining of a specific antibody against the PLC isozyme, PLC-delta, demonstrated that this enzyme was abnormally accumulated in neurofibrillary tangles (NFT), the neurites surrounding senile plaque (SP) cores, and neuropil threads in AD brains. Western blot analysis confirmed that PLC-delta was concentrated in the paired helical filament (PHF)-rich fraction of AD brains. Antibodies to other PLC isozymes did not produce positive immunostaining of these pathologic structures. Moreover, diffuse and amorphous deposits of PLC-delta were found to precede the accumulation of fibrillary deposits. These results suggest that PLC-delta accumulation is a crucial event that ultimately may contribute to the formation of PHF.