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.
Shimohama
S
S
Department of Neurology, Faculty of Medicine, Kyoto University, Japan.
Homma
Y
Y
Suenaga
T
T
Fujimoto
S
S
Taniguchi
T
T
Araki
W
W
Yamaoka
Y
Y
Takenawa
T
T
Kimura
J
J
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology; D000906:Antibodies / Q000276:immunology; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D001923:Brain Chemistry; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D008247:Lysosomes / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D010738:Type C Phospholipases / Q000032:analysis / Q000276:immunology / Q000378:metabolism*
D000906:Antibodies; D007527:Isoenzymes; D010738:Type C Phospholipases