Nicotinic Acetylcholine Receptors and Alzheimer's Disease

Amyloid plaques, neurofibrillary tangles and inflammatory events are the key neuroanatomical markers of Alzheimer’s Disease (AD). In addition, AD is accompanied by a loss of neurons expressing nicotinic acetylcholine receptors (nAChRs) in many parts of the brain.

Pathology and Symptoms of Alzheimer's Disease

There is compelling evidence pointing to the involvement of nicotinic acetylcholine receptors (nAChRs) in AD. As an example,

• Amyloid peptides, which are found abundantly in the brains of AD patients, can inhibit nicotine-induced Ca2+ currents into cells expressing nAChRs,
• The Aβ 1-42 peptide, the most prominent component of amyloid plaques, tightly binds to the α7 nAChR subtype, thereby activating it at low concentrations, and inactivating it (probably by desensitization) at high concentrations, potentially inducing apoptotic death of the cells expressing nAChRs,
• Nicotine is able to compete with Aß in binding to nAChRs, and appears to protect against Aß-induced neurotoxicity, and
• nAChRs and amyloid plaques are co-localized in Alzheimer brains.

Although it is firmly established that nicotinic acetylcholine receptors represent essential elements of brain plasticity and cell survival, their exact involvement in AD pathology and neuroprotective mechanisms remains to be fully elucidated.