Aberrant expression of the glutamate transporter excitatory amino acid transporter 1 (EAAT1) in Alzheimer's disease.
Glutamate-mediated toxicity has been implicated in the neurodegeneration observed in Alzheimer's disease. In particular, glutamate transport dysfunction may increase susceptibility to glutamate toxicity, thereby contributing to neuronal cell injury and death. In this study, we examined the cellular localization of the glial glutamate transporter excitatory amino acid transporter 1 (EAAT1) in the cerebral cortex of control, Alzheimer's disease, and non-Alzheimer dementia cases. We found that EAAT1 was strongly expressed in a subset of cortical pyramidal neurons in dementia cases showing Alzheimer-type pathology. In addition, tau (which is a marker of neurofibrillary pathology) colocalized to those same pyramidal cells that expressed EAAT1. These findings suggest that EAAT1 changes are related to tau expression (and hence neurofibrillary tangle formation) in dementia cases showing Alzheimer-type pathology. This study implicates aberrant glutamate transporter expression as a mechanism involved in neurodegeneration in Alzheimer's disease.
Scott
Heather L
HL
Departments of Biochemistry and Physiology and Pharmacology, University of Queensland, Brisbane, Queensland, Australia, 4072. scotth@biosci.uq.edu.au
Pow
David V
DV
Tannenberg
Anthony E G
AE
Dodd
Peter R
PR
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000032:analysis; D002540:Cerebral Cortex / Q000378:metabolism* / Q000473:pathology; D015161:Dementia, Multi-Infarct / Q000378:metabolism / Q000473:pathology; D027341:Excitatory Amino Acid Transporter 1 / Q000032:analysis / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D020961:Lewy Body Disease / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D017966:Pyramidal Cells / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000032:analysis / Q000096:biosynthesis
D015415:Biomarkers; D027341:Excitatory Amino Acid Transporter 1; D016875:tau Proteins