Scientists from the UK’s Dementia Research Institute at University College London (UCL) and VIB-KU Leuven have discovered the cause of the death of neurons in Alzheimer’s disease (AD), opening up potential avenues to develop new treatments for the condition.

The researchers found that a programmed form of cell death, known as necroptosis, is initiated when neurons are exposed to amyloid plaques and tau tangles.

The researchers created a new model to replicate and connect AD hallmark features – amyloid plaques, tau tangles, and death of neurons – by implanting both healthy human and mouse neurons into the brains of AD mouse models.

They discovered that only human neurons displayed Alzheimer’s features, including tau tangles and neuronal cell loss.

These findings suggest that humans have specific factors that play in Alzheimer’s that standard mouse models cannot replicate, as their neurons are more resilient to amyloid pathology.

Upon further research, the team revealed that necroptosis was activated within the model, which led to the death of neurons.

They observed higher levels of a molecule called MEG3, caused by amyloid and tau build-up inducing inflammation in the brain, in human neurons, which triggered the process of necroptosis.

Additionally, the study discovered that by reducing MEG3 and preventing necroptosis, the researchers were able to prevent the death of cells.

Professor Bart Strooper, group leader at the VIB-KU Leuven Center for Brain and Disease Research and the UK Dementia Research Institute at UCL, says the findings from the study "open up promising avenues for potential therapies targeting AD, alongside traditional approaches aimed at amyloid and tau" and could lead to a "whole new line of drug development".

Dr Susan Kohlhaas, from Alzheimer's Research UK, said: "This discovery is important because it points to new mechanisms of cell death in AD that we didn't previously understand and could pave the way for new treatments to slow or even stop disease progression in the future."

AD is a progressive condition recognised as the most common type of dementia that affects around 900,000 people in the UK.

Additional research is needed to understand how MEG3 triggers the pathway of necroptosis.
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