Alterations in Neuropeptide Systems in Alzheimer’s Disease

The high concentration of neuropeptides in cortical interneurons, their neurotransmitter or neuromodulator roles, and their colocalization with conventional neurotransmitters have served as an impetus for studies of neuropeptide systems in Alzheimer’s disease (AD). Substantial progress in biochemical characterization of AD has been obtained from studies of neurotransmitter systems in postmortem tissue. Alterations in cholinergic neurons have been demonstrated consistently in patients with histologically verified AD. The most reproducible finding has been that of marked reductions in the activity of choline acetyltransferase (ChAT), a marker of intact cholinergic neurons, in the neocortex and hippocampus as well as in the nucleus basalis of Meynert (substantia innominata) in AD (see Davies and Wolozin 1987 for review). Similarly, alterations in noradrenergic and serotonergic neurons (Adolfsson et al. 1979; Tomlinson et al. 1981; Perry et al. 1981a; Gottfries etal. 1983; Yates etal. 1983 a; Arai et al. 1984a; Iversenetal. 1984) in AD have been demonstrated, although a recent study suggested that these deficits may be apparent only in severely demented patients exhibiting widespread neuronal loss, while cholinergic deficits may occur in more moderate cases of AD (Palmer et al. 1987).