Neuronal Loss and Neurotransmitter Receptor Alterations in Alzheimer’s Disease

Abstract

Alzheimer's disease (AD) is characterized by degeneration of neurons in several neurotransmitter-specific systems (Price et al., in press; Whitehouse et al., in press b). Alterations in telencephalic presynaptic cholinergic markers, such as choline acetyltransferase (ChAT), have been most closely linked to the severity of clinically apparent dementia and to the density of senile plaques and neurofibrillary tangles (Blessed et al., 1968; Wilcock et al., 1982). The anatomical basis for the presynaptic cholinergic dysfunction in amygdala, hippocampus, and neocortex appears to be loss of neurons in the basal forebrain cholinergic system (Chl-4 system) (Whitehouse et al., 1981; Whitehouse et al., 1982; Arendt et al., 1983; Candy et al., 1983; Tagliavini and Pilleri, 1983). This system is composed of neurons in the medial septum (Chi), diagonal band of Broca (Ch2), and the nucleus basalis of Meynert (nbM) (Ch4) (Hedreen et al., 1983; Mesulam et al., 1983). A role for acetylcholine in dementia is supported by animal experiments in which anticholinergic drugs and anatomical lesions of the Chl-4 system have been shown to produce memory dysfunction (Deutsch, 1971; Aigner et al-, 1984; Olton et al., 1984), In this paper, I will review: our recent clinical studies of neuronal loss in this system in AD and related disorders; evidence for neuronal loss in other neural systems; studies of neurotransmitter receptor alterations in AD; and recent characterizations of cholinergic receptor alterations.