Interindividual differences in the levels of the glutamate transporters GLAST and GLT, but no clear correlation with Alzheimer's disease

Alzheimer's disease is a common progressive neurodegenerative disease of un known etiology, Several different pathological processes have been identifi ed in the brains of Alzheimer patients. To determine if reduced glutamate u ptake is a contributing factor, we have measured the levels of the glutamat e transporter proteins GLAST (EAAT1) and GLT (EAAT2) in human autopsy sampl es. The postmortem proteolysis of these proteins turned out to be fairly ra pid. Brains from 10 Alzheimer and 10 control patients were therefore obtain ed with a relatively short postmortem delay (5 hr on average). GLT (N-termi nal and central parts), GLAST (C-terminal), glial fibrillary acidic protein (GFAP) and inositol (1,4,5)-triphosphate (IP3)- receptor immunoreactivitie s were determined in the cingulate and inferior temporal gyri by immunoblot ting, The Na+-dependent "binding" of D-[H-3]aspartate and the glutamate upt ake after solubilization and reconstitution in liposomes were determined fo r comparison. An individual variation in GLAST and GLT levels was found, bu t no significant correlation with Alzheimer's disease, except for a 14% low er ratio of N-terminal to central GLT immunoreactivity (P < 0.04), The leve ls of GLAST and GLT showed negative correlation in agreement with the idea that these proteins are differentially regulated. In conclusion, Alzheimer' s disease brains can have both normal and reduced levels of GLAST and GLT. J. Neurosci. Res. 55:218-229, 1999. (C) 1999 Wiley-Liss, Inc.