Increased connectivity in early Alzheimer’s is lowered by cancer drug in the lab

(Press-News.org) Neuroscientists at King’s College London have pinpointed a mechanism behind the increased neural connectivity observed in the very early stages of Alzheimer’s disease.  

Published in Translational Psychiatry, the study also demonstrated that a cancer medication has the potential to reduce this hyperconnectivity. 

The research, funded by Alzheimer's Society and conducted in brain cells of rats, showed that low levels of the protein amyloid-beta could induce hyperconnectivity and this pattern closely resembled changes seen in the brains of people with mild cognitive impairment (MCI). Amyloid-beta is thought to be instrumental in Alzheimer’s disease, where it creates plaques – or sticky clumps of amyloid-beta proteins – around the neurons. 

These new findings suggest that low levels of amyloid-beta alone are enough to trigger early, disease-relevant changes in how brain cells connect. 

Previous research has found that the number of connections (synapses) between neurons in the brain increases during the earliest stages of Alzheimer’s disease and it has been shown that these initial changes correlate with mild cognitive impairment (MCI) in patients. MCI is characteristic of the early stages of Alzheimer's disease, prior to widespread cell death and memory loss.  

Kaiyu Wu, first author on the study from the Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King’s College London said: “The results of this new study contribute to a new way of thinking about Alzheimer’s disease. Instead of starting with synapse loss, the disease may begin with too many poorly organized connections, combined with subtle but targeted changes in protein production. Over time, this unstable state could make brain circuits more vulnerable, eventually leading to the synaptic failure and cognitive decline seen in later stages of the disease.” 

This new study shows that low doses of amyloid-beta protein over a  period of five days can cause hyperconnectivity between brain cells. The study also identifies changes in levels of 49 proteins, including its own precursor, that work together to increase the connectivity in the early stages of the disease. 

 “This suggests the system may act as a self-reinforcing loop in which amyloid-beta promotes conditions that lead to even more amyloid-beta,” explained Kaiyu Wu. 

Previous work from the same research group at King’s led by Professor Karl Peter Giese has identified a drug target that might be able to alter protein production associated with synapse increases. This target, MAP kinase interacting kinase (MNK), is also the target of the clinically licensed drug eFT508, currently used in cancer clinical trials. The drug has not been used to investigate or treat Alzheimer’s disease before. 

The team found that eFT508 prevented the increase in connectivity caused by amyloid-beta exposure. They also found that the drug was also able to restore 70% of the altered protein production after amyloid-beta exposure. 

Professor Giese, senior author on the paper and Professor of Neurobiology of Mental Health at IoPPN, King’s College London said: “Our research suggests a promising drug treatment for memory loss in mild cognitive impairment and early Alzheimer’s disease. Next, our findings need to be validated first in suitable animal models, before clinical trials can commence.” 

Michelle Dyson, Chief Executive Officer at Alzheimer’s Society said: “This study builds our knowledge of brain cell changes in early-stage Alzheimer’s disease and suggests that with intervention we may be able to counteract some of these changes as Alzheimer’s disease develops. 
  
“It’s important to note this was very early-stage work in animal cells rather than human participants so more research is needed. But it shows how drug repurposing is a promising avenue for us to explore if we are to end the devastation of dementia - a condition that affects around one million people in the UK.   

“For decades, cancer research has set the benchmark for what can, and should, be done for dementia. Research will beat dementia and we look forward to seeing how this research progresses.” 

Low concentrations of amyloid-beta oligomers induce synaptogenesis characteristic for mild cognitive impairment and alter the de novo proteome by Wu, K. et al. is published in Translational Psychiatry DOI 10.1038/s41398-026-03905-x https://doi.org/10.1038/s41398-026-03905-x  

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