Changes in platelet phospholipase C protein level and activity in Alzheimer's disease

We have previously demonstrated that PLC-delta was abnormally accumulated in autopsied brains with Alzheimer's disease (AD). As nonneuronal tissue involvement in AD is also suggested and PLC activity is reduced in AD platelets, we examined the changes of the protein level of PLC-delta and its enzyme activity in platelets taken from patients with AD and age-matched controls. PLC-delta in human platelets was detected as a 72 kDa protein using a specific antibody against PLC-delta. Western blots revealed that the protein level of PLC-delta was significantly higher in the cytosolic fraction prepared from AD platelets compared to controls. We investigated the activity of PLC-delta which hydrolyzes phosphatidylinositol and found that the PLC-delta activity in the cytosolic fraction from AD platelets was significantly reduced compared to the control. This finding that the enzyme activity per PLC-delta molecule is reduced in AD platelets is consistent with the study using Alzheimer brains. These results suggest that aberrant phosphoinositide metabolism is present in nonneuronal tissues as well as the brains of patients with AD.