Abstract

Background: Alzheimer disease (AD) is a neurodegenerative disorder occurring in elderly people and leading to the loss of memory, practical and speaking habits. In spite of extensive efforts undertaken during the last decades, there is still no generally recognized explanation of the origin and primary pathological changes leading to AD development. Consequently, the suggested pharmacological approaches to treat the AD patients are mostly symptomatic and do not stop the disease progression. Neuroinflammation and cholinergic deficit usually accompany AD development. However, their impact in AD progression still waits for being properly recognized.

Objective: The present review aims at analysis of the role of inflammation and nicotinic acetylcholine receptors, primarily of α7 subtype (α7 nAChRs), in the development of AD in humans and AD-like symptoms in experimental animals.

Results: The reviewed data describe the involvement of α7 nAChRs in the AD pathogenesis, in particular, through their interaction with amyloid-β, maintenance of brain cell viability and regulation of neuroinflammation. They also delineate the role of α7-specific (auto)antibodies in stimulating neuroinflammation, memory impairment in mice and AD progression in humans.

Conclusion: Neuroinflammation is suggested as a primary stimulus sufficient to trigger accumulation of pathologically processed amyloid-β, degeneration of cholinergic neurons and memory impairment. The level of α7 nAChR expression in the brain is critical for supporting the resistance to inflammatory and apoptogenic agents. The data presented may be a basis to create a new strategy for preventing and, possibly, slowing AD development in humans.

Keywords: Alzheimer disease, nicotinic acetylcholine receptor, inflammation, antibody.