Therapeutic Approach to Improve Hyperexcitation in Alzheimer’s Disease


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Seonil Kim

At A Glance

Researchers at Colorado State University have developed a combination treatment of selective nicotinic acetylcholine receptor agonists to reverse hippocampal hyperactivity, which is believed to be a major contributor to cognitive decline in Alzheimer’s disease (AD).  Given that neuronal hyperexcitability in the pre-symptomatic stages of AD may play an important role in disease progression, co-activation of selective nicotinic acetylcholine receptors is an innovative and novel therapeutic strategy.

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Reference No.:  2019-108


​A prominent Alzheimer’s disease (AD) pathology is the loss of cholinergic neurons and nicotinic acetylcholine receptors throughout the brain. Thus, current FDA-approved drugs for AD aim to increase acetylcholine levels in the brain, but they are not very effective – possibly due to non-selective stimulation of receptors. Indeed, there are discrepancies between the effects of acetylcholine receptor stimulation on cognitive function in different studies. Nearly 30 subtypes of neuronal nicotinic acetylcholine receptors having been reported. Further studies are needed in order to better understand the role of each receptor agonist or co-activation of receptors in cognitive function and develop more effective pharmacological treatments for AD.

Importantly, neurotoxic beta-amyloid peptide (Aβ) disrupts neuronal activity via interaction with nicotinic acetylcholine receptors. However, how Aβ specifically interacts with each subtype of receptors to produce an overall effect on neuronal function remains unclear. Thus, there is an urgent current and future need for understanding neurobiological mechanisms of how Aβ-induced disruption of nicotinic acetylcholine receptor in the hippocampal network, which ultimately impairs learning and memory in AD, so that research efforts can be focused on strategies aiming to modify the disease process.

  • Data indicates co-activation of selected nicotinic receptors inhibited and reversed hyperexcitation
  • Can potentially prevent drastic cognitive decline found in late stage AD
  • Early treatment of Alzheimer’s Disease
  • Treatment of hyperexcitability

Sun, Julianna L., et al. “Co-Activation of Selective Nicotinic Acetylcholine Receptors Is Required to Reverse Beta Amyloid–Induced Ca2+ Hyperexcitation.” Neurobiology of Aging, Elsevier, 19 Sept. 2019,

Last updated: May 2020

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