GLUTAMATE TRANSPORTER ALTERATIONS IN ALZHEIMER-DISEASE ARE POSSIBLY ASSOCIATED WITH ABNORMAL APP EXPRESSION

Recent studies have shown that deficient functioning of glutamate tran sporters (GTs) in Alzheimer disease (AD) might lead to neurodegenerati on. The main objectives of the present study were to determine which G T subtype is most affected in AD and to asses to what extent altered G T function is associated with abnormal amyloid precursor protein (APP) expression. While EAAT2-immunoreactivity (IR) was decreased in AD fro ntal cortex, EAAT1- and EAAT3-IR were unaffected; mRNA levels for all 3 GTs were not affected. Decreased EAAT2-IR was associated with decrea sed GT activity. EAAT2-IR inversely correlated with EAAT2 mRNA levels, suggesting that in AD, GT expression alterations occur due to disturb ance at the post-transcriptional level. EAAT2-IR was inversely correla ted with APP770 mRNA. In addition, GT activity directly correlated wit h APP695 mRNA and total APP protein levels, and inversely correlated w ith APP751/770 mRNA levels. This study supports the notion that astrog lial EAAT2 is affected in AD and abnormal functioning and/or processin g of APP might play an important role in this process.