GALANINERGIC INNERVATION OF THE CHOLINERGIC VERTICAL LIMB OF THE DIAGONAL BAND (CH2) AND BED NUCLEUS OF THE STRIA TERMINALIS IN AGING, ALZHEIMER-DISEASE AND DOWN-SYNDROME

The galanin (GAL) containing peptide fiber system circuit which innerv ates acetylcholine containing basal forebrain neurons has been shown t o hypertrophy and hyperinnervate remaining cholinergic Ch4 perikarya i n Alzheimer's disease (AD). The present study examined whether a simil ar hyperinnervation occurs within the cholinergic vertical limb of the diagonal band nucleus (Ch2), a portion of the basal forebrain which, unlike Ch4, exhibits only modest degeneration in AD. Furthermore, we e valuated whether GAL hyperinnervation occurs within the basal forebrai n in Down's syndrome, a genetic disorder with extensive AD-like pathol ogy including cholinergic basal forebrain neuron degeneration. The pre sent study revealed that virtually all Ch2 neurons were GAL immunonega tive. However, this region was innervated by GAL immunoreactive (ir) i nterneurons and fibers associated with a major galaninergic pathway wh ich travels through the substantia innominata enroute to the hypothala mus, bed nucleus of the stria terminalis as well as vertical limb of d iagonal band nucleus. GAL-ir fibers coursing within this fiber bundle hypertrophied in AD relative to age matched controls and the Down's ca ses. Within the putative Ch2 terminal zones in AD, many of the remaini ng cholinergic neurons were hyperinnervated by GAL despite the modest reduction in Ch2 neurons. In contrast, GAL-ir fibers were not hypertro phied in Down's syndrome despite extensive cholinergic cell loss withi n Ch4. Taken together these findings suggest that extensive cholinergi c basal forebrain cell loss alone is not sufficient to trigger the bas al forebrain GAL plasticity response found in AD.