Phospholipase pathway in Alzheimer's disease brains: decrease in Galphai in dorsolateral prefrontal cortex

There is substantial evidence that G-protein-associated signaling pathways in the brain are altered in Alzheimer's disease (AD). Using quantitative immunoblotting we find a significant decrease in Galphai levels in every AD case examined compared to controls (mean Galphai level in AD was 43.5+/-7.4% of control). Galphao levels were slightly decreased, but Galphaq and betagamma were normal. Phospholipase C-beta1, but not gamma1, levels were also decreased. Total phospholipase C activity and ceramide levels were not changed. Thus, in AD, there is impairment in the Galphai-associated signaling pathway in neurons.