The Alpha7-Beta2 Nicotinic Receptor and Its Roles in Amyloid Beta Pathology in Alzheimer's Disease

Accumulation of beta amyloid peptide, including Aβ1-42, is a hallmark of Alzheimer's disease (AD). In the early stages of AD, neuronal death is observed in the septum and the hippocampus of the brain. This neuronal death causes memory and cognitive dysfunction which are clinical manifestations of AD. A newly-discovered neurotransmitter receptor subtype, the α7β2 nicotinic acetylcholine receptor (α7β2-nAChR) is expressed in the septum and the hippocampus of the rodent and human brain. This pentameric receptor has similar functional characteristics to α7-nAChR, a more prevalent subtype. It has been shown that α7-nAChRs mediate internalization of Aβ1-42. Others have shown that Aβ1-42 internalization may cause neuronal dysfunction and death. The aims of the present study are to determine if α7β2-nAChR mediates internalization of Aβ1-42, if this is toxic to the cells, and if it affects intracellular calcium activity. We have used multiphoton microscopy to show internalization of the peptide in SH-EP1 cells expressing α7β2-nAChR and α7-nAChR, and live/dead assays for measuring cell death. Epi-fluorescence microscopy and calcium dyes are being used to compare calcium activity of cells expressing these receptors. These are preliminary steps toward determining the pathogenic molecular mechanisms of neuronal dysfunction and cell death in early stages of AD.