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expert reaction to restoring memory function in an Alzheimer’s disease mouse model

Research published in Brain demonstrates a possible method of restoring memory function in mice with familial Alzheimer’s disease.

Clive Ballard, Professor of Age-Related Diseases at the University of Exeter Medical School, said:

“Epigenetics is the study of the way genes are regulated, which controls how they behave – it’s an exciting area of research in Alzheimer’s disease as unlike our genes, these processes can be influenced by external factors, meaning they could be promising targets for future treatments. At Exeter this is a key area of research and we now know epigenetics plays a key role in Alzheimer’s disease. It’s exciting to see drugs coming through that target these mechanisms, but we do need to be cautious. Many studies that have looked promising in mice have failed to translate into benefits in humans, so we need more research to see if this has real potential to reverse memory loss in people.”

Prof. Dr. Tiago Outeiro, Professor of Neurodegeneration, Newcastle University, said:

“Alzheimer’s disease, as other neurodegenerative disorders, cannot be simply explained due to genetics, as most cases are sporadic, thereby resulting from the interplay between genes and the environment. In this context, “epigenetics”, or what is beyond the genes, is emerging as an interesting concept to explain the complexity of these disorders, as epigenetics influences gene expression in multiple ways.

“We and others have shown that several genes associated with Alzheimer’s are prone to epigenetic regulation.

“In this study, the authors used one of the existing mouse models of Alzheimer’s disease to assess the effect of one type of epigenetic modification, known as histone methylation, on the expression of specific proteins which are required for normal brain function and memory consolidation. Interestingly, they found that the Alzheimer’s mice displayed epigenetic alterations which were also present in brain tissue from individuals who died with Alzheimer’s. Moreover, they report that inhibition of the pathways involved in this type of epigenetic modification was protective in mice, restoring their memory function.

“While this study is exciting and promising, it confirms already existing evidence highlighting that epigenetics may be an important player in the complexity of Alzheimer’s disease. Additional studies will be required to further validate these findings in other animal models, and may open novel avenues for future clinical trials in Alzheimer’s patients.”

Dr James Pickett, Head of Research at Alzheimer’s Society, said:

“The brain changes that take place in someone with Alzheimer’s disease are incredibly complex. Taking an epigenetic approach – changing the way our cells read the genes in our DNA – has the potential to target, and even reverse, these complex changes. But, before we get ahead of ourselves, it’s crucial to note that this study has only shown promise in mice so far, and the results were short-lasting.

“Epigenetics holds a lot of potential for dementia research. With no new treatment for dementia in the past 15 years, and the number of people living with the condition on the rise, it’s an approach that our researchers are using to understand the underlying causes of Alzheimer’s.”

Dr Rosa Sancho, Head of Research at Alzheimer’s Research UK, said:

“We know a complex mix of genetics and lifestyle are behind diseases like Alzheimer’s, and epigenetics represents a way that these forces can interact. One of the most exciting aspects of epigenetic research is that the changes are potentially reversible, and this study highlights how targeting an epigenetic change could help improve brain function in mice with features of Alzheimer’s disease.

“These interesting findings in mice now need to be taken forward in studies in people, to explore whether they could form the basis of a future treatment approach for people with Alzheimer’s disease.  

“Alzheimer’s is a complex disease and it is important to tackle it from as many different angles as possible. Drugs that target epigenetic changes are already available for people with cancer and Alzheimer’s Research UK is funding research into epigenetics to further understand this important process and how it can be used to treat diseases like Alzheimer’s.”

Prof. Frances A Edwards, Professor of Neurodegeneration, University College London, said:

“If it is a model which expresses familial AD mutations and has plaques and not tangles, then the memory effects probably have little to do with Alzheimer’s disease. Humans with plaques and no tangles don’t have diagnosable memory deficits. Where changes occur also depends strongly on which mouse model. If it is a transgenic mouse, the promoter for the transgenes will greater influence where in the brain changes occur and in many cases the memory effects are probably due to overexpression of APP which results in over production of a range of active peptides in addition to Abeta. The observation in human brain is interesting but of course the functional effects of that particular change cannot be tested.”

Prof. John Hardy FMedSci, Professor of Neuroscience, UCL, said:

“In previous studies memory function in mouse models has not predicted memory function in humans.”

‘Inhibition of EHMT1/2 rescues synaptic and cognitive functions for Alzheimer’s disease.’ by name of Zheng et al. was published in Brain at 14:00 UK time on Tuesday 22nd January 2019

All our previous output on this subject can be seen at this weblink: http://www.sciencemediacentre.org/tag/alzheimers/

Declared interests

Prof. Dr. Tiago Outeiro: “No, I do not have any conflicts of interest to declare.”

None others received.

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