The role of nerve growth factor (NGF) in Alzheimer's Disease (AD) and aging has been investigated with various techniques. The underlying hypothesis leading to these investigations has been that well-established cholinergic deficits observed in AD and aging may be due to defective NGF function. This study focusses on the NGF receptorsputatively located on cholinergic neurons. The applicant proposes to investigate whether there is an NGF receptor dysfunction detectable in aging animals. The number of 125I-NGF labelled receptors in various relevant rat brainregions will be monitored as a function of age in rats. Special attentionwill be paid to possible changes in the projection areas (i.e. terminal NGF receptors) versus changes in cell body NGF receptors. A second directionof the study is to investigate whether there are multiple brain NGF receptorsor, possibly, two states of one NGF receptor. These latter studies will involve using solubilized receptors and monitoring the antigenic potentialof the brain NGF receptors as assessed using NGF receptor antibody developedfor peripheral NGF receptors. The effect of age on multiple NGF receptorswill follow, given that reliable assays for multiple NGF receptors or statesare developed.
