Neuroscientists at King’s College London have pinpointed the mechanism behind the increased neural connectivity observed in the very early stages of Alzheimer’s disease.
Published in translational psychiatrythis study also demonstrated that cancer drugs may alleviate this hyperconnectivity.
The study, funded by the Alzheimer’s Society and carried out in rat brain cells, showed that low levels of the protein amyloid beta can induce hyperconnectivity, a pattern that closely resembles changes seen in the brains of people with mild cognitive impairment (MCI). Amyloid beta produces plaques, or sticky clumps of amyloid beta protein, around neurons and is thought to be involved in Alzheimer’s disease.
These new findings suggest that even low levels of amyloid beta are sufficient to trigger early disease-related changes in the way brain cells connect.
Previous studies have found that the number of connections (synapses) between neurons in the brain increase during the early stages of Alzheimer’s disease, and these early changes have been shown to correlate with mild cognitive impairment (MCI) in patients. MCI is characteristic of the early stages of Alzheimer’s disease, preceding widespread cell death and memory loss.
The results of this new study contribute to new ways of thinking about Alzheimer’s disease. The disease may not begin with the loss of synapses, but a combination of too many poorly organized connections and subtle but targeted changes in protein production. Over time, this unstable state can make brain circuits more vulnerable and ultimately lead to synaptic failure and cognitive decline seen in later stages of the disease. ”
Kaiyu Wu, first author of the study, Institute of Psychiatry, Psychology and Neuroscience, King’s College London
This new study shows that administering low doses of amyloid beta protein over five days can cause hyperconnectivity between brain cells. The study also identified changes in the levels of 49 proteins, including unique precursors, that work together to increase connectivity during early stages of disease.
“This suggests that this system may act as a self-reinforcing loop in which amyloid beta promotes conditions that cause even more amyloid beta,” Kaiyu Wu explained.
Previous work by the same research group at King’s University, led by Professor Karl-Peter Gies, has identified drug targets that can alter protein production associated with synapse proliferation. This target, MAP kinase-interacting kinase (MNK), is also the target of the clinically approved drug eFT508, which is currently being used in cancer clinical trials. This drug has never been used to research or treat Alzheimer’s disease.
The research team found that eFT508 prevented the increase in connectivity caused by amyloid beta exposure. They also found that the drug could restore 70% of protein production altered after amyloid beta exposure.
Professor Gies, senior author of the paper and IoPPN Professor of Mental Health Neurobiology at King’s College London, said: “Our study suggests a promising drug treatment for memory loss in mild cognitive impairment and early Alzheimer’s disease. Next, we first need to test our findings in suitable animal models before starting clinical trials.”
Michelle Dyson, chief executive of the Alzheimer’s Society, said: “This study builds on our knowledge of changes in brain cells in early stages of Alzheimer’s disease and suggests that interventions may be able to counteract some of these changes as the disease progresses.”
“It is important to note that this is very early stage research in animal cells rather than human participants, so further research is needed. However, it shows that drug repurposing is a promising avenue for us to end the scourge of dementia, which affects around one million people in the UK.”
“For decades, cancer research has set the standard for what can and should be done in the fight against dementia. Research is what beats dementia, and we look forward to seeing how this research progresses.”
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Reference magazines:
Wu, K. Others. (2026). Low concentrations of amyloid beta oligomers induce synaptogenesis and alter the de novo proteome characteristic of mild cognitive impairment. translational psychiatry. DOI: 10.1038/s41398-026-03905-x, https://www.nature.com/articles/s41398-026-03905-x.
