Altered Expression of G‐protein subunits and GRKs in Alzheimer's Disease

Disturbed neurotransmitter signaling has been reported in Alzheimers disease (AD), however molecular changes underlying those disturbances in AD are not agreed upon. We hypothesize that altered G‐proteins, G‐protein receptor kinases (GRKs), and orphan G‐proteins are altered in AD. To test this hypothesis, we measured protein and mRNA levels of samples of G‐proteins, G‐protein receptor kinases (GRKs), and orphan G‐proteins in postmortem human frontal cortex (Brodmann area 9) tissue from AD patients and age matched control subjects. mRNA levels of Gγ, GRK2 and GRK5, but not GRK3 were decreased while Gβ mRNA was increased in AD compared to controls. Membrane and cytosol protein levels were not different in AD except for Gβ which was higher in the cytosolic fraction for AD. The expression of orphan G‐proteins in AD with matched controls will be compared and their roles will be discussed. Gβ and Gγ mRNA levels are altered in AD. Differences in GRK levels suggest interference with protein translocation from the cytosol to membranes of neurons in AD. This may play a role in neurotransmitter neurosignaling in AD patients. This work was supported by the Intramural Research Program of the National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA and by a grant from the Harvard Brain Bank, Boston, MA for providing the postmortem brain samples under PHS Grant number R24MH068855.