Protein kinase C-zeta activity but not level is decreased in Alzheimer's disease microvessels.

While there is considerable evidence demonstrating altered activity of the major isoforms of protein kinase C (PKC) in the vasculature and neurons of Alzheimer disease (AD) brains, little is known about the activity and/or levels of the atypical PKC isoforms. The objective of this study is to compare PKC-zeta activity and level in cerebral microvessels isolated from AD brains with microvessels from the brains of nondemented age-matched controls. Measurements of the kinase activity reveals that the PKC-zeta activity is significantly (P < 0.01) lower in AD brain microvessels compared with vessels from control brain. Despite this decrease in enzyme activity, the level of PKC-zeta, assessed by Western blot, is significantly (P < 0.01) elevated in AD microvessels. These data demonstrate significant and divergent changes in the PKC-zeta activity and level in the microcirculation of the AD brain and suggest that aberrant regulation of microvascular PKC-zeta could contribute to the abnormal signaling mechanisms at the blood-brain barrier in the AD brain.