Ca2+‐Dependent and Ca2+‐Independent Protein Kinase C Changes in the Brains of Patients with Alzheimer's Disease

We examined protein kinase C (PKC) activity in Ca2+-dependent PKC (Ca2+-dependent PKC activities) and Ca2+-independent PKC (Ca2+-independent PKC activities) assay conditions in brains from Alzheimer's disease (AD) patients and age-matched controls. In cytosolic and membranous fractions, Ca2+-dependent and Ca2+-independent PKC activities were significantly lower in AD brain than in control brain. In particular, reduction of Ca2+-independent PKC activity in the membranous fraction of AD brain was most enhanced when cardiolipin, the optimal stimulator of PKC-epsilon, was used in the assay; whereas Ca2+-independent PKC activity stimulated by phosphatidylinositol, the optimal stimulator of PKC-delta, was not significantly reduced in AD. Further studies on the protein levels of Ca2+-independent PKC-delta, PKC-epsilon and PKC-zeta in AD brain revealed reduction of the PKC-epsilon level in both cytosolic and membranous fractions, although PKC-delta and PKC-zeta levels were not changed. These findings indicated that Ca2+-dependent and Ca2+-independent PKC are changed in AD, and that among Ca2+-independent PKC isozymes, the alteration of PKC-epsilon is a specific event in AD brain, suggesting its crucial role in AD pathophysiology.