Loss of inositol 1,4,5-trisphosphate receptor sites and decreased PKC levels correlate with staging of Alzheimer's disease neurofibrillary pathology

Inositol 1,4,5-trisphosphate (IP 3), inositol 1,3,4,5-tetrakisphosphate (IP 4) and protein kinase C (PKC) play important roles in the phosphoinositide hydrolysis signal transducing pathway. Several studies have shown severe deficits in both IP 3 receptor levels and PKC levels and activity in Alzheimer's disease brain, although the relationship of these changes to disease pathology is poorly understood. In the present study, we determined the autoradiographic localization of [ 3 H] IP 3 and [ 3 H] IP 4 binding to their calcium mobilizing receptor sites and [ 3 H] phorbol 12,13-dibutyrate ( [ 3 H] PDBu) binding to PKC in sections of entorhinal cortex/hippocampal formation and cerebellum from 24 cases that had been staged for Alzheimer's disease-related neurofibrillary changes and amyloid deposition according to Braak and Braak [Acta Neuropathol. Berl., 82 (1991) 239–259]. Results indicated that [ 3 H] IP 3 binding showed a trend towards a decline with staging for neurofibrillary changes in the entorhinal region (0.05< P