Reduction in TrkA-immunoreactive neurons is not associated with an overexpression of galaninergic fibers within the nucleus basalis in Down's syndrome

Down's syndrome (DS) individuals develop neuropathological features similar to Alzheimer's disease (AD), including degeneration of cholinergic basal f orebrain (CBF) neurons. In AD a reduction in CBF/trkA-containing neurons ha s been suggested to trigger a hyperexpression of galaninergic fibers within the nucleus basalis subfield of the basal forebrain, The present study exa mined the interrelationship between reductions in CBF/trkA-containing neuro ns and the overexpression of galaninergic fibers within the nucleus basalis in DS, Within the nucleus basalis stereologic evaluation revealed a 46% re duction in the number of trkA-immunopositive neurons, whereas optical densi ty measurements displayed a nonsignificant 18% reduction in neuronal trkA i mmunoreactivity in DS as compared with age-matched controls. Western blot a nalysis also showed a significant reduction in cortical trkA protein levels in DS. A semiquantitative examination of galaninergic fibers in the nucleu s basalis revealed only a modest hypertrophy of galaninergic fibers within the nucleus basalis in DS. The present findings indicate a significant redu ction in trkA within the nucleus basalis and cortex with only a moderate hy pertrophy of galaninergic fibers in DS. These observations suggest that DS may not be an exact genetic model for investigation of changes in the AD ba sal forebrain.