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Abstract: The present study correlates the severity of dementia in Alzheimer’s disease with the degree of neuropathology present in the nucleus basalis of Meynert. We assessed neurofibrillary tangles, neuronal loss and morphometric changes in 21 patients with Alzheimer’s disease who underwent extensive neuropsychological testing before death. We report a highly significant correlation between scores in the psychological tests and all of the neuropathological markers examined within the nucleus basalis of Meynert. The test that correlated most closely with these morphological measures was Folstein’s Mini Mental State. Among the different neuropathological changes, the number of neurofibrillary tangles was strongly correlated with the degree of dementia. We also provide evidence for a differential involvement of the three subdivisions of the nucleus basalis in Alzheimer’s disease neuropathology. The posterior subdivision, which provides a substantial cholinergic input to the parahippocampal gyrus, was the more profoundly affected. Taken together, these results point to an important participation of the nucleus basalis in dementia of the Alzheimer type. In addition, the strong correlation between neuropathological changes and neuropsychological scores indicates the reliability of these tests in assessing the progression of the disease.

Galanin immunoreactive fibers hypertrophy and hyperinnervate remaining cholinergic basal forebrain neurons within the septum–diagonal band complex in Alzheimer's disease. The present investigation determined whether a similar hyperinnervation of galanin immunoreactive fibers occurs following intraparenchymal injections of ibotenic acid within the cholinergic medial septum or diagonal band nucleus in young adult rats. Sections through the medial septum and the diagonal band were either concurrently immunostained for galanin and the low-affinity p75 neurotrophin receptor (an excellent marker of cholinergic basal forebrain neurons) or single stained for choline acetyltransferase. Following chemical lesion, an increase in the density of galanin immunoreactivity was seen within the medial septum on the lesion, as opposed to the contralateral control side. In contrast, within diagonal band-lesioned animals, the increase in galanin immunoreactivity was low to moderate. In either lesion paradigm we did not observe hyperinnervation of remaining cholinergic basal forebrain neurons. In fact, there was no correlation between the galanin hypertrophy and the amount of cholinergic cell loss. We hypothesize that galanin hyperinnervation within the cholinergic basal forebrain may provide a protective effect by down-regulating acetylcholine release following brain insult.