Nicotinic Acetylcholine Receptor Signaling in Neuroprotection

Accumulation of amyloid β protein (Aβ) in the brain causes cognitive impairment in Alzheimer’s disease (AD). The nature of the relationship between smoking and AD or dementia has been controversial. However, a recent meta-analysis revealed that smoking is a risk factor for AD. With regard to nicotinic acetylcholinergic receptors (nAChRs), both AD and control patients that smoke have been reported to show an increase in ³H-cytisine (an α4β4 nAChR agonist) binding in the temporal cortex. The α7 nAChR is also a key factor in AD pathology, particularly in relation to internalization of Aβs. Furthermore, there are many reports showing the neuroprotective effects of nicotine. The internalization of Aβ may lead to Aβ clearance in the brain. We hypothesized that an extracorporeal system that rapidly removes Aβ from the blood may accelerate Aβ clearance from the brain. We have reported that (1) several medical materials including hemodialyzers can effectively remove blood Aβ, (2) the concentrations of blood Aβs decreased during hemodialysis, (3) removal of blood Aβ enhanced Aβ influx into the blood (ideally from the brain), resulting in maintenance or improvement of cognitive function, and (4) Aβ deposition in the brain of hemodialysis patients was significantly lower than in controls. Smoking affected blood Aβ removal efficiencies and brain atrophy. We believe this Extracorporeal Blood Aβ Removal Systems (E-BARS) may contribute as a therapy for AD.