Phospholipase pathway in Alzheimer's disease brains: decrease in G(alpha i) 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 im munoblotting we find a significant decrease in G(alpha i) levels in every A D case examined compared to controls (mean G(alpha i) level in AD was 43.5 +/- 7.4% of control). G(alpha o) levels were slightly decreased, but G(alph a q) and beta gamma were normal. Phospholipase C-beta 1, but not gamma l, l evels were also decreased. Total phospholipase C activity and ceramide leve ls were not changed. Thus, in AD, there is impairment in the G(alpha i)-ass ociated signaling pathway in neurons. (C) 1999 Elsevier Science B.V. All ri ghts reserved.