Morphometric immunochemical analysis of neurons in the nucleus basalis of Meynert in Alzheimer's disease

Abstract

In Alzheimer's disease there is a reported loss of large cells in the cholinergic nucleus basalis of Meynert. It has been suggested, however, that there may be neurons in the nucleus basalis in Alzheimer's disease which are atrophied and therefore difficult to distinguish form neuroglia by size. This has important therapeutic implications and we have attempted to clarify the situation using a neuron-specific antiserum directed against neuron-specific enolase (NSE). Sections of nucleus basalis were stained using this antiserum and the neuronal cross-sectional area was measured. A profile of neuronal distribution with area was obtained, by image analysis, and compared in controls and patients with Alzheimer's disease. A significant 29% overall loss of neurons was found in Alzheimer's disease with a much greater loss (61%) of large neurons and concurrent increase (59%) in small neurons. Analysis of variance showed significant reduction in mean cross-sectional neuronal area as a consequence of this shift in frequency towards a preponderance of small cells. It is suggested that in the nucleus basalis in Alzheimer's disease, large neurons are not completely lost; many are shrunken and thus excluded from the previous studies of large cells counted in Nissl-stained material. That there is partial preservation of these neurons makes it more likely that cholinergic dysfunction, characteristic of Alzheimer's disease, will be amenable to neurotrophic influence.