Researchers Unveil Neuron Death Mechanism in Alzheimer’s Disease
A groundbreaking study has revealed the mechanism behind neuron death in Alzheimer’s disease (AD). The study, led by Professor Bart De Strooper at VIB-KU Leuven and the UK Dementia Research Institute (UK DRI) at UCL, and Dr. Sriram Balusu at VIB-KU Leuven, identified a programmed form of cell death called necroptosis in neurons exposed to amyloid plaques and tau tangles, two hallmark proteins associated with AD. Furthermore, the researchers identified an RNA gene called MEG3 as a potential key player in this process. These findings provide promising pathways for future treatments.
Necroptosis is a programmed cell death process that is initiated in neurons exposed to amyloid plaques and tau tangles. The researchers observed that levels of the RNA gene MEG3 were significantly increased in human neurons, as seen in Alzheimer’s patients. This suggests that MEG3 plays a critical role in the neuron death mechanism observed in AD.
To study AD more effectively, the research team created a new model by implanting both healthy human and mouse neurons into the brains of AD mouse models. Remarkably, only the human neurons displayed AD features, including tau tangles and significant neuronal cell loss. This indicates that there may be human-specific factors at play in Alzheimer’s that standard mouse models cannot replicate.
By utilizing their new model, the researchers discovered that necroptosis was activated in the human neurons, leading to cell death. Additionally, the presence of MEG3 alone was sufficient to trigger necroptosis in human neurons in a laboratory setting. However, by reducing MEG3 levels and preventing necroptosis, the researchers were able to prevent the death of cells.
This significant breakthrough sheds light on the previously unknown mechanisms underlying Alzheimer’s disease. Understanding the role of MEG3 and the process of necroptosis in neuronal loss provides new avenues for potential therapies targeting AD. This discovery complements traditional approaches aimed at amyloid and tau, the hallmark proteins of the disease.
Professor De Strooper highlights the importance of these findings, stating, “Our study sheds light on the previously murky waters of Alzheimer’s disease, revealing a potential key player in neuronal loss—the RNA gene MEG3, and the process of necroptosis. These findings are an important step forward in furthering our understanding of the basic mechanisms underlying this complex and often misunderstood disease.”
The research paper titled “MEG3 activates necroptosis in human neuron xenografts modeling Alzheimer’s disease” is published in the journal Science.