Preservation of noradrenergic neurons in the locus ceruleus that coexpressgalanin mRNA in Alzheimer's disease

Galanin (GAL) innervation is hypertrophied in the basal forebrain and corte x of patients with Alzheimer's disease (AD). Increased GAL could exacerbate the cognitive and behavioral deficits of AD because GAL acts as an inhibit ory modulator of cholinergic and noradrenergic neurotransmission. The locus ceruleus (LC) may be a source of increased GAL in AD because (a) GAL is co expressed in a subset of LC neurons, (b) GAL expression is up-regulated wit h neuronal injury, and (c) the LC undergoes extensive degeneration in AD. T herefore, we have used in situ hybridization histochemistry to measure GAL gene expression in the LC of AD patients and sex- and age-matched nondement ed controls. Despite the extensive loss of norepinephrine neurons with AD, GAL mRNA-expressing neurons in the LC did not differ between groups. This r esulted in a significant increase in the percentage of neuromelanin-pigment ed cells that coexpressed GAL in AD patients compared with controls. These findings wise the possibility that the increased incidence of GAL expressio n among remaining LC neurons contributes to the hyperinnervation of GAL fib ers in AD. Furthermore, GAL may be neuroprotective in the LC.