Upregulated excitatory amino acid transporter 1 (EAAT1) expression in the human medial temporal lobe in Alzheimer's disease.

Abstract

Alzheimer's disease (AD) is a growing health problem worldwide, particularly in the developed world due to an ageing population. Glutamate excitotoxicity plays a major role in the pathophysiology of AD, and glutamate re-uptake is controlled by excitatory amino acid transporters (EAATs). The EAAT2 isoform is the predominant transporter involved in glutamate reuptake, therefore EAAT1 has not been the focus of AD research. We investigated the layer-specific expression of EAAT1 in human medial temporal lobe regions such as the hippocampus, subiculum, entorhinal cortex and superior temporal gyrus, using fluorescent immunohistochemistry and laser scanning confocal microscopy in human post-mortem tissue. We observed low EAAT1 immunoreactivity in control cases, but upregulated labeling in AD across several brain regions of the medial temporal lobe. Significantly higher integrated density in AD cases was observed in the str. oriens and str. radiatum of the CA2 region, the str. pyramidale of CA3, and the str. moleculare and str. granulosum of the DG. Labeling of EAAT1 appeared astrocytic in nature, showing close association with astrocytic processes in AD cases. We also report that a higher EAAT1 density was positively correlated with the age of AD cases, but this relationship was not observed in control cases. Overall, our results indicate an upregulation of EAAT1 across several hippocampal subregions and layers in AD cases, indicating a potential physiological role for this transporter that needs further investigation.