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.
Young
R A
RA
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 230 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6082, USA.
Talbot
K
K
Gao
Z Y
ZY
Trojanowski
J Q
JQ
Wolf
B A
BA
D000368:Aged; D000544:Alzheimer Disease / Q000378:metabolism*; D001923:Brain Chemistry / Q000502:physiology; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000032:analysis / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000201:enzymology; D017397:Prefrontal Cortex / Q000166:cytology / Q000201:enzymology*; D015398:Signal Transduction / Q000502:physiology; D010738:Type C Phospholipases / Q000378:metabolism*
D010738:Type C Phospholipases; D019206:GTP-Binding Protein alpha Subunits, Gi-Go