IMMUNOCYTOCHEMICAL DISTRIBUTION OF PEPTIDERGIC AND CHOLINERGIC FIBERSIN THE HUMAN AMYGDALA - THEIR DEPLETION IN ALZHEIMERS-DISEASE AND MORPHOLOGIC ALTERATION IN NONDEMENTED ELDERLY WITH NUMEROUS SENILE PLAQUES

As part of an ongoing investigation devoted to understanding the patho genesis of senile plaques, we employed histochemical and immunocytoche mical techniques to examine the distribution and cytologic features of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), somato statin (SOM), neurotensin (NT) and substance P (SP) containing fibers and neurons within the amygdala of: (1) patients with Alzheimer's dise ase (AD); (2) age-matched non-demented controls (NC); and (3) a group of non-demented cases, who upon postmortem neuropathologic examination exhibited sufficient numbers of senile plaques to be classified as AD . This latter group was referred to as high plaque non-demented (HPND) . For every case, the distribution of immunolabeled fibers and neurons were determined for each transmitter throughout the various subnuclei of the amygdala. In addition, in the AD and HPND cases the topographi c distribution of senile plaques was determined throughout the amygdal a using thioflavine-S and Bielschowsky silver methods. In the amygdala , the distribution and density of senile plaques were not bound by con ventional cytoarchitectural groupings but rather were most dense in th e ventromedial regions of the amygdala with decreasing density in dors al and lateral directions. Importantly, the density and distribution o f senile plaques failed to correlate with the normal topography and/or density of the various peptidergic or cholinergic fibers within the a mygdala. The finding that plaques do not correlate with the topographi c distribution of any specific transmitter system suggests that plaque s likely do not arise from the degeneration of a single neurotransmitt er system (i.e., the cholinergic system). However, the finding that in AD a transmitter is most markedly depleted in regions of greatest pla que density, suggests certain constituents of the plaque (e.g. beta-am yloid) may be contributing to the degeneration of local fibers. The ex tent to which a transmitter was depleted in AD patients varied conside rably among those four investigated with the cholinergic and NT system s displaying the most dramatic reductions, followed by SP and SOM. Des pite these differential reductions in fiber density, all four neurotra nsmitters were found localized within dystrophic neurites and in most instances these dystrophic neurites were associated with thioflavine-p ositive senile plaques. In contrast to the AD cases, the HPND cases we re characterized by no significant reductions in immunolabeled fibers, although immunostained dystrophic neurites were very prevalent in the HPND cases. These data suggest that dystrophic neurites occur very ea rly in the disease process and likely precede the actual loss of fiber s when or if it occurs. Moreover, the absence of any significant loss of labeled fibers in the HPND cases versus the marked reduction of fib ers in the AD cases underscores the putative importance of fiber and/o r synaptic loss as an anatomical correlate to dementia.