Galanin receptor plasticity within the nucleus basalis in early and late Alzheimer's disease: an in vitro autoradiographic analysis

Abstract

Hypertrophy of fibers containing galanin (GAL), the inhibitory neurotransmitter of acetylcholine, occur on remaining cholinergic nucleus basalis neurons in late stage Alzheimer's disease (AD). The present investigation evaluated whether changes in the number of GAL receptors (GALR) were detectable within the nucleus basalis in the early or late stage of AD when compared to age-matched controls. Postmortem neuropathological specimens were obtained at autopsy from three groups: late AD, early (possible) AD, and normal (age-matched controls) human subjects. Autoradiography of GALR binding was performed on human brain sections from each of the three groups. Analysis of autoradiographic images show no change in the distribution of [125]hGAL binding sites in early AD cases throughout the nucleus basalis. In contrast, the number of [125]hGAL binding sites was increased over the anterior nucleus basalis subfield in late stage AD. A region-of-interest densitometric analysis of the anterior nucleus basalis in the late stage AD cases depict an increase in the number of [125]hGAL binding sites by approximately two-three-fold when compared to normal (age-matched controls). Quantitative measures of [125]hGAL binding densities were not significantly different in the anterolateral, intermediate or posterior nucleus basalis subsectors of early or late stage AD when compared to age-matched controls. These observations show that the occurrence of overexpression of GALRs coincide with earlier reports showing galaninergic fibers hyperinnervating surviving cholinergic basal forebrain neurons in late stage AD.