There is growing evidence implicating the monoamines in the cognitive disorders associated with neurodegenerative diseases. Few studies, however, have succeeded to investigate the role of the monamine transporters, the nore pinephrine transporter (NET) and serotonin transporter (5-HTT), in neurodegeneration. While such studies are promising, the major reason they have not been conducted could be attributed to the absence of a suitable radioligands for labeling these sites. In previous studies, 3H-desipramine and 3H-imipramine have been used to label NET and 5-HTT respectively. However, these ligands exhibit low specific binding (approximately 40%) and bind to two sites: a high affinity site and a low affinity site. We have recently developed 3H-nisoxetine (3H-NIS) as a useful radioligand for labeling NET. 3H-NIS binds with high affinity (Kd 0.7nM) and specificity to a single population of NET sites in rat cortical homogenates and tissue sections. More recently, we have reported an age-related reduction in NET binding in the LC taken from normal subjects ranging in ages from 19-80 as well as reduced 3H-NIS binding to NET sites in the LC of AD patients. The present study uses the highly specific and selective ligands, 3H-NIS and 3H-cyanoimipramine (3H-CNIMI), and the technique of quantitative autoradiography (QAR) to measure NET and 5-HTT sites in cortical and sub-cortical regions in brains from Alzheimer's Disease patients.
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