New UCL Alzheimers Research Sparks Hope for Future Therapies

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UCL researchers discover how neurons die in Alzheimer's disease. What does this mean for potential future therapies?

A new model has revealed the key player in programmed neuronal cell death. Is this the beginning of a new pathway to treat Alzheimer’s disease?

Since the discovery of amyloid plaques and tau tangles as defining features of Alzheimer's disease (AD) pathology, it has been a public health priority to discover the link between the presence of these misfolded proteins and neuronal cell loss with the onset of AD symptoms.

On the 14th of September, a team of researchers from the UK and Belgium, led by Professor Bart De Stopper (UK Dementia Research Institute UCL and VIB-KU Leuven) and Dr Sriram Balasu (VIB-KU Leuven) published a breakthrough discovery on Science. 

The team was able to identify an RNA gene called MEG3, which is involved in programmed neuronal cell death, also known as necroptosis, a process used by the brain to get rid of unwanted or dying cells. This discovery was possible thanks to the creation of a new AD mouse model that contained both healthy human and mouse neurons. The addition of healthy human neurons allowed the researchers to understand that human neurons are more susceptible to tau tangles and amyloid plaques when compared to mouse neurons and led to the discovery that AD presents human-specific characteristics that were never observed before. This includes the contribution of MEG3.

So, how is MEG3 involved in neuronal cell death? It appears that the inflammation caused by the presence of the above-mentioned misfolded proteins, in particular tau tangles, trigger the activation of MEG3, which translates into elevated levels of the molecule in AD patients. The research team observed that the presence of high levels of MEG3 alone was enough to trigger the start of necroptosis. Furthermore, they were able to demonstrate that lowering the levels of MEG3 resulted in the prevention of necroptosis, leading to a reduction in neuronal cell loss. 

This breakthrough not only highlights the involvement of MEG3 as a human-specific factor in the symptomatology of AD but also offers a new model to develop and test potential disease-modifying treatments that will slow or hopefully prevent the degeneration of neurons. Professor Bart De Stopper commented, “These findings are an important step forward in furthering our understanding of the basic mechanisms underlying this complex and often misunderstood disease.”

Future treatments currently look towards preventing the loss of cognitive functions in AD patients via short-term dosing and aim to substitute current treatments that have a focus on the reduction of symptoms and which have so far displayed disappointing results. Professor Tara Spires-Jones from the University of Edinburgh concluded that “many steps are needed to understand how to harness this discovery as an effective AD treatment”. However, Professor Bart De Stopper concluded, “Our findings open up promising avenues for potential therapies targeting Alzheimer’s disease, alongside traditional approaches aimed at amyloid and tau.”

Despite the development of a whole new line of drugs to treat neuronal degeneration being years away, the advancement of scientific research and the promise of a better quality of life brings hope to AD patients and their families worldwide who face the daily emotional and physical burdens of the disease.