Cerebral microvessels in Alzheimer's have reduced protein kinase C activity.

Protein kinase C (PKC) is an important intracellular signalling enzyme. Numerous studies have suggested that alterations in this enzyme occur in aging and dementia. The objective of this study was to examine PKC in the cerebral microcirculation in aging and Alzheimer's disease. PKC activity, amount, and isoform distribution were analyzed in microvessels from adult and aged rodents as well as from Alzheimer patients and nondemented elderly controls. PKC activity was lower in Alzheimer vessels than in vessels from control brains, despite the presence of similar levels of PKC enzyme. In contrast, both activity and enzyme levels in young and aged rats were comparable. The beta-isoform was present in both rat and human microvessels and there were no age- or disease-related alterations. The loss in activity in cerebromicrovascular PKC in Alzheimer's suggest that perturbations in phosphorylation signalling cascades may exist at the Alzheimer blood-brain barrier.