Cholinergic neurons were studied by immunohistochemistry, with an antiserum against choline acetyltransferase (ChAT), in the basal forebrain (Ch1 to Ch4) of four patients with Alzheimer's disease (AD) and four control subjects. ChAT-positive cell bodies were mapped and counted in Ch1 (medial septal nucleus), Ch2 (vertical nucleus of the diagonal band), Ch3 (horizontal nucleus of the diagonal band) and Ch4 (nucleus basalis of Meynert). Compared to controls, the number of cholinergic neurons in AD patients was reduced by 50% on average. The interindividual variations in cholinergic cell loss were high, neuronal loss ranging from moderate (27%) to severe (63%). Despite the small number of brains studied, a significant correlation was found between the cholinergic cell loss and the degree of intellectual impairment. To determine the selectivity of cholinergic neuronal loss in the basal forebrain of AD patients, NPY-immunoreactive neurons were also investigated. The number of NPY-positive cell bodies was the same in controls and AD patients. The results (1) confirm cholinergic neuron degeneration in the basal forebrain in AD and the relative sparing of these neurons in some patients, (2) indicate that degeneration of cholinergic neurons in the basal forebrain contributes to intellectual decline, and (3) show that, in AD, such cholinergic cell loss is selective, since NPY-positive neurons are preserved in the basal forebrain.

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The somatostatinergic innervation, and by comparison that of neuropeptide Y, was examined by immunocytochemistry, in the hippocampal formation of 6 patients with clinically and neuropathologically confirmed diagnosis of Alzheimer's disease (AD) and 4 matched controls. The quantitative assessment of the somatostatin and neuropeptide Y immunoreactive cell perikarya was conducted on regularly spaced sections covering the span of the whole hippocampus and parahippocampal cortex. The estimated total number of somatostatin or neuropeptide Y containing neurons was similar in the hippocampal formation of patients with AD and controls. By contrast, the density of the somatostatinergic fibers and terminals as estimated by the optical density of the somatostatin neuropil, significantly decreased by 30-45% in all the hippocampal subregions and the parahippocampal cortex, whereas the density of the neuropeptide Y immunoreactive neuropil significantly decreased (45%) only in the parahippocampal cortex. Numerous enlarged fibers containing somatostatin or neuropeptide Y, some of which were observed within senile plaques, were detected in the brain of patients with AD. These data suggest that in AD, somatostatin and neuropeptide Y containing cell bodies in the hippocampus and parahippocampal gyrus are anatomically preserved, in spite of an altered terminal field.

The somatostatinergic innervation, and by comparison that of neuropeptide Y, was examined by immunocytochemistry, in the hippocampal formation of 6 patients with clinically and neuropathologically confirmed diagnosis of Alzheimer's disease (AD) and 4 matched controls. The quantitative assessment of the somatostatin and neuropeptide Y immunoreactive cell perikarya was conducted on regularly spaced sections covering the span of the whole hippocampus and parahippocampal cortex. The estimated total number of somatostatin or neuropeptide Y containing neurons was similar in the hippocampal formation of patients with AD and controls. By contrast, the density of the somatostatinergic fibers and terminals as estimated by the optical density of the somatostatin neuropil, significantly decreased by 30-45% in all the hippocampal subregions and the parahippocampal cortex, whereas the density of the neuropeptide Y immunoreactive neuropil significantly decreased (45%) only in the parahippocampal cortex. Numerous enlarged fibers containing somatostatin or neuropeptide Y, some of which were observed within senile plaques, were detected in the brain of patients with AD. These data suggest that in AD, somatostatin and neuropeptide Y containing cell bodies in the hippocampus and parahippocampal gyrus are anatomically preserved, in spite of an altered terminal field.