Decreased brain [3H]inositol 1,4,5-trisphosphate binding in Alzheimer's disease.

Inositol 1,4,5-trisphosphate (IP3) receptor binding sites were studied in autopsied brains from 10 subjects with dementia of the Alzheimer type (DAT) and 10 age-matched controls. In the parietal cortex and hippocampus, there was a 50-70% loss of [3H]IP3 binding whereas no significant changes were observed in frontal, occipital and temporal cortices, caudate or amygdala. Scatchard analysis confirmed a reduction in receptor density rather than a change in affinity. Since muscarinic receptors are robustly coupled to IP3 formation, our data demonstrate abnormalities beyond the muscarinic receptor recognition site in DAT.