High selective expression of α7 nicotinic receptors on astrocytes in the brains of patients with sporadic Alzheimer's disease and patients carrying Swedish APP 670/671 mutation: a possible association with neuritic plaques

Abstract

In the present study, we have investigated the expression of nicotinic acetylcholine receptors (nAChRs) on astrocytes and neurons in the hippocampus and temporal cortex of subjects carrying the Swedish amyloid precursor protein (APP) 670/671 mutation (APPswe), patients with sporadic Alzheimer's disease (AD), and age-matched control subjects. Significant increases in the total numbers of astrocytes and of astrocytes expressing the α7 nAChR subunit, along with significant decreases in the levels of α7 and α4 nAChR subunits on neurons, were observed in the hippocampus and temporal cortex of both APPswe and sporadic AD brains. Both of these phenomena were more pronounced in APPswe than sporadic AD cases. Furthermore, the number of [ 125I]α-BTX binding sites (α7 nAChR) in the temporal cortex of the APPswe brain was significant lower than in the younger control group, reflecting the lower neuronal level of α7 nAChR. The increase in the level of expression of α7 nAChR on astrocytes was positively correlated with the extent of neuropathological alternations, especially the number of neuritic plaques, in the AD brain. The elevated expression of α7 nAChR on astrocytes might participate in Aβ cascade and formation of neuritic plaques, thereby playing an important role in the pathogenesis of AD.