Science AMA Series: I'm Mark Dallas, a Lecturer in Cellular and Molecular Neuroscience at the School of Pharmacy, University of Reading. I carry out research to better understand what goes wrong in our brains in complex diseases such as Alzheimer’s disease and I’m here today to talk about it. AMA!

Abstract

Hi Reddit,

My name is Mark Dallas, I am a Lecturer in Cellular and Molecular Neuroscience at the School of Pharmacy, University of Reading, where I have worked for 4 years, after postdoctoral positions at the University of Leeds. I am Academic Co-ordinator for the Alzheimer’s Research UK Oxford Network, Neuroscience Theme Lead for the Physiological Society and on the editorial board of Physiology News.

My main research interest is working to understand the mechanism by which our brains change that leads to devastating diseases such as Alzheimer’s disease. Today 850,000 people in the UK live with dementia, and currently there is not treatment that will prevent, cure or slow down it’s progression. My experiments are looking at the so called glial cells within the brain and how they respond in the face of stressful stimuli. I believe these non-neuronal cells could provide insight and even early indications as to the onset of disease, well before clinical symptoms. Here we use a diverse array of model systems for cultured cells to animal models of disease. Only by building from cells to systems will we truly understand what is happening in our brains, the most complex computer of all.

It is my opinion that we still need some animal research to undercover the complexities of the brain and this research should be in concert with other non-animal experimental approaches. This will be fundamental to our research efforts aimed at combating Alzheimer’s disease. I wholly support the research community’s efforts to carry out this research under strict guidance that ensures responsible, high-quality research and requires the highest possible welfare standards, driven by application of the 3Rs. Indeed as part of my own research we are exploring the use of human cells as more appropriate models of brain disease.

Only by engaging the public in our research activities and how we use animals in science, will we address concerns and misunderstandings. This is something I am actively involved in through many outreach activities, including today.

During World Alzheimer’s Month, I’m here to talk about the wonders of our brains, and how they are disrupted by disease, what research is telling us about Alzheimer’s disease, the use of animal research in tackling human diseases, and I'll be back to answer questions at 10 AM ET (3 pm BST), Ask Me Anything!

This AMA is organised by Understanding Animal Research.

Thanks for all your insightful questions and I hope you found it useful. I certainly enjoyed the AMA session! I am signing off now. Best wishes, Mark

You mention that it is important to talk about how we use animals in science. What do you mean by that? What are the common misconceptions about animal model work?

divvyflax

I think it is important to be open about our scientific research and the models we use and to inform the public. Common misconceptions are often around the numbers used and the regulations surrounding use.


Hi

Thanks for doing this AMA!

With both sides of my family with a history of Alzheimer's, I ask this with some self-interest. I've been following the resent research on the development of novel treatments, vaccines and genetic therapies.

I'll ask the obvious question - how close are we to a cure?

Thanks in advance!

mvea

Thanks for the question; while scientists tend to hide away from the word ‘cure’, these are exciting times in dementia research. There is double the number of clinical trials taking place in the field and we are all hopeful that these will provide a disease modifying treatment within the next 10 years. As a basic scientist there are several new avenues (e.g. cell types, new proteins) being explored which will hopefully enter clinical trials in the near future.


Hi Mark, and thank you for doing this AMA!

What are your thoughts on "Type 3 diabetes" in the context of Alzheimer's disease?

  • How robust is the research that suggests that insulin resistance in the brain is occurring in a sizable fraction of AD patients?

  • What are the implications for synaptic health (synapses use lots of glucose)?

  • Is there a biological mechanism by which you can envision brain insulin resistance being linked to cognitive impairment?

Thanks!

SirT6

Yes there is growing awareness of a link between diabetes and dementia, while not my direct area of research it is a growing area of interest for neuroscientists and physiologists. We know that energy metabolism is compromised in AD, and evidence indicates insulin and insulin receptors are deficient in AD.

Indeed communication between nerve cells requires a lot of energy. If you deprive nerves cells of the necessary support, communication fails which leads to a breakdown in signalling within the brain.

There are many theories around this; however scientists are still working on these pathways to provide evidence linking the two pathways.


Thank you for doing this AMA!

My understanding is that exercise is protective for aging brains, both in the presence and the absence of diseases such as Alzheimer's. Is that still a pretty well-supported view? Since many rodent animal models seem to live their lives in the absence of exercise opportunities, is this something we should push to change in how lab research is conducted . . . or maybe that makes them a better model for a lot of us?

neurobeegirl

Exercise is beneficial to the brain as well as our hearts, and studies highlight this. In the context of Alzheimer’s disease there is no definitely evidence to say that exercise prevents the disease. A package of healthy lifestyle choices (e.g. diet, exercise) will reduce the risk of developing dementia. The recent Lancet article indicated 9 lifestyle changes that could reduce the risk.

It is an interesting observation with regards to animal models; this is very dependent on the study design. Some studies incorporate exercise regimes to look at specific aspects of exercise.


My Grandfather suffered from Alzheimers and it's truly an awful disease.

I just have a question around genetically modified animal models. My knowledge is limited but, as far as I understand it, these GM models have significantly helped advance the understanding of the disease and I just wonder if there's more that can be done to further refine them as more is learnt?

Your research sounds fascinating and I wish you the very best of luck.

LCresser

The use of GM models has indeed provided a wealth of information for a host of diseases, including complex neurological disorders. It is true to say that these are limited and don’t reflect the human disease in all aspects.

Researchers are now looking to the potential of human stem cells to provide a better representation of the human disease, this research is in its infancy and models are still being validated. A combination of both models will give us the best insight into the disease and be critical to tackling dementia.


Hi Dr. Dallas,

Thank you for taking time for the AMA today.

What are the current thoughts on amyloid plaques and neurofibrillary tangles and the pathogenesis of AD? Are they just a byproduct or are they involved in the pathogenesis?

Also, since we don't have great biomarkers for diagnosing AD, what do you think about the possibility that we could actually be lumping different diseases under AD and thus muddying our understanding of the pathogenesis and treatment?

MRIson

I think both are implicated in the disease and the evidence in the literature points to this; it is an evolving theory and the lack of success with therapeutics targeting amyloid alone highlights it is not the only protein involved. You can reduce amyloid load, but cognitive deficits are still maintained. This is why further research into dementia, supported by Alzheimer’s Research UK, is required to better understand the interactions between not only tau and amyloid but other signalling pathways that have been implicated in pathogenesis.

In terms of bio-markers, no clear signal has emerged and it is true that AD in itself can present with different pathological hallmarks and clinical presentation. While AD is an umbrella, the disease is very much and individual one and our interactions with carers and people living with dementia highlight this.


Hello! Thanks for doing this AMA.

What kind of imaging technology is facilitating this research? How well do these techniques transfer from animal models to imaging the human body?

shiruken

There are different types of imaging that are used in dementia research. Human imaging studies which include MRI and PET scans can provide insight into structural and metabolic changes in the brain. This is something I don’t carry out myself.

Scientists also look at imaging different cells (nerve cells, microglia) using fluorescent probes to understand the effects of disease. These can be generated from animal models or indeed more recently human stem cells.

Both modalities provide different information that help to better understand what is happening in our brains, with a view to developing new medicines.


I keep reading that current research suggests that Alzheimer’s disease is linked to diet. Is this accurate?

rich115

There are links and see some other posts about diabetes and dementia. Eating a balanced and healthy diet is going to beneficial for your brain and reduce the risk of dementia.


Hello, I am curious about testing to find out if someone will/does have Alzheimer's. Is there such a thing? Is Alzheimer's passed down generationally, is it genetic? Both my maternal and paternal grandmothers had Alzheimer's, which makes me worry about both my parents, my children, and myself. I would also I like to ask about possible preventative measures. What has been shown (to date) to reduce the symptoms in the animals being tested on? Diet, exercise, medication? What can I do now to help my family?

Correao

There are tests available, however I would discuss this with your GP in the first instance.

As for preventative measures see the dementia charities (Alzheimer's Research UK or Alzheimer's Society) for latest information. Recently, 9 lifestyle choices have been identified to play a role in the risk of developing dementia.


Thanks for being here today! When studying Alzheimer's in human brains, how representative is RNA/protein levels to the true disease state, given that samples can only be collected post mortem? Is degradation a significant complicating factor?

p1percub

This is a technical question to which I cannot answer as my research does not involve human samples. Best advice is to look at the MRC Brain Bank website for further information.


Thanks for doing this AMA. Do you see much of a role for stem cells in treating Alzheimer's and, if so, what challenges do you foresee administering them to affected parts of the brain?

towerhil

I don't think we are in a position to suggest stem cells as a treatment for AD. The research has not been done and indeed raises several challenges, not least ethical issues.

Where I think stem cells will advance our understanding is by providing better models for the human disease and provide a more robust platform for testing new medicines. This is work that myself and colleagues within the Alzheimer's Research UK Oxford Network are contributing to.


What is your opinion on aducanumab as a potential treatment for Alzheimer's?

Vaqolm

We will have to wait and see, promising data from initial studies but a long way of being in the clinic. See comment from ARUK.


How do you feel about the claim that Alzheimer's could be called "Type III Diabetes"?

thebiggestfish012

See my reply to SirT6 above


Do you think we will be able to effectively treat these diseases soon?

deadagain124

Please see reply to mvea above


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