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 unknown etiology. Several different pathological processes have been identified in the brains of Alzheimer patients. To determine if reduced glutamate uptake is a contributing factor, we have measured the levels of the glutamate transporter proteins GLAST (EAAT1) and GLT (EAAT2) in human autopsy samples. The postmortem proteolysis of these proteins turned out to be fairly rapid. Brains from 10 Alzheimer and 10 control patients were therefore obtained with a relatively short postmortem delay (5 hr on average). GLT (N-terminal and central parts), GLAST (C-terminal), glial fibrillary acidic protein (GFAP) and inositol (1,4,5)-triphosphate (IP3)-receptor immunoreactivities were determined in the cingulate and inferior temporal gyri by immunoblotting. The Na+-dependent "binding" of D-[3H]aspartate and the glutamate uptake after solubilization and reconstitution in liposomes were determined for comparison. An individual variation in GLAST and GLT levels was found, but no significant correlation with Alzheimer's disease, except for a 14% lower ratio of N-terminal to central GLT immunoreactivity (P < 0.04). The levels 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.
Beckstrøm
H
H
Department of Anatomy, Institute of Basic Medical Sciences, University of Oslo, Norway.
Julsrud
L
L
Haugeto
O
O
Dewar
D
D
Graham
D I
DI
Lehre
K P
KP
Storm-Mathisen
J
J
Danbolt
N C
NC
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism*; D000595:Amino Acid Sequence; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001692:Biological Transport; D004591:Electrophoresis, Polyacrylamide Gel; D027342:Excitatory Amino Acid Transporter 2; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D011180:Postmortem Changes; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D013702:Temporal Lobe / Q000378:metabolism