Reduction in p140-trkA receptor protein within the nucleus basalis and cortex in Alzheimer's disease
It has been hypothesized that the diminished transport of nerve growth factor (NGF) seen within cholinergic basal forebrain (CBF) neurons in Alzheimer's disease (AD) results from a defect in the expression of its high- affinity trkA receptor. The present study used an anti-human trkA-specific monoclonal antibody (mAb 5C3) that recognizes the NGF docking site, combined with quantitative optical densitometry, to evaluate whether expression of the trkA protein is altered within the nucleus basalis and its cortical projection sites in AD. In normal aged humans, trkA immunoreactivity revealed a continuum of positive neurons extending throughout all CBF subfields. In addition, trkA-positive neurons were scattered throughout the olfactory tubercle and striatum. These regions also displayed intense trkA neuropil staining. Although fewer in total number, remaining CBF perikarya in AD displayed a significant decrease in trkA levels relative to aged controls. Biochemical analysis revealed a significant reduction in trkA protein within both the nucleus basalis and the frontal cortex in AD relative to aged controls. In contrast, trkA levels in the caudate nucleus were unaffected. The decrease in trkA protein in conjunction with our recent observations that the message for trkA is reduced within individual CBF neurons in AD supports the concept that defects in the production and/or utilization of the trkA receptor may be a key event mediating degeneration of NGF-responsive CBF neurons in this disease.
Digital Object Identifier (DOI)
Mufson, Elliott J.; Lavine, Natalie; Jaffar, Syed; Kordower, Jeffrey H.; Quirion, Rémi; and Saragovi, H. Uri, "Reduction in p140-trkA receptor protein within the nucleus basalis and cortex in Alzheimer's disease" (1997). Translational Neuroscience. 1933.