SYSTEMATIC REGIONAL VARIATIONS IN THE LOSS OF CORTICAL CHOLINERGIC FIBERS IN ALZHEIMERS-DISEASE

The loss of cortical cholinergic fibers in Alzheimer's disease was inv estigated using choline acetyltransferase immunohistochemistry and ace tylcholinesterase histochemistry. Within both the normal and Alzheimer 's cerebral cortex, the two methods revealed an identical pattern of f iber staining. In the normal brain, cholinergic fiber density was high est in limbic and paralimbic cortical zones, intermediate in most sens ory-motor and association zones, and lowest within the primary visual and visual association areas of the occipital lobe. In general, suprag ranular cortical layers contained a higher density of cholinergic fibe rs, and most of these were oriented vertically. In Alzheimer's disease , an overall 55% loss of cortical cholinergic fibers was detected. The re was, however, marked regional variations in the extent of this loss in different cortical areas. Cortical areas within the temporal lobe, particularly the temporal association areas, displayed a dramatic los s of cholinergic fibers. By contrast, the anterior cingulate cortex, p rimary visual, primary somatosensory, and primary motor cortex display ed a relative preservation of cholinergic fibers. As a whole, greater loss of cholinergic fibers was detected in supragranular layers and in fibers oriented vertical to the cortical surface. These results indic ate that cholinomimetic therapies are likely to have different effects on cholinergic transmission in various cortical areas. The precise me chanisms that lead to the regional variations in cortical cholinergic denervation in Alzheimer's disease remain to be elucidated.