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Uncovering the role of the immune system in dementia with Lewy bodies: Jay Amin

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Jay Amin is an Alzheimer’s Research UK Clinical Research Fellow at the University of Southampton (UK). We talked to him about balancing his roles as a clinician and a researcher and found out more about his current study looking at the role of neuroinflammation in dementia with Lewy bodies.

Can you introduce yourself and tell us a little about your career to date?

I studied medicine at the University of Southampton and during my junior doctor training I specialized in old age psychiatry, with an interest in diagnosing and treating individuals with dementia. It was at about this time that I was given the opportunity to do an Academic Clinical Fellowship with the National Institute of Health Research (UK), which allowed me to take my first steps into research. The fellowship got me involved in clinical trials for dementia and working with postmortem brain tissue in Alzheimer’s disease. Following this, I applied for and was awarded a Clinical Research Fellowship with Alzheimer’s Research UK, which I’m currently working on.

What sparked your interest in getting involved with academic research in addition to your day-to-day medical career?

I was really struck by the lack of treatments we have for individuals with Alzheimer’s disease when I started my specialist training in clinical care with dementia. I was able to offer all sorts of other supportive options to patients, like helping them get enough care and enough psychological support, but actually there are only a handful of medications we can prescribe, and sometimes people get side effects. It was the frustration of not really being able to offer patients and carers anything that will either halt or reverse the disease.

The other factor was taking those first steps into research and getting some exposure to it fairly early on in my career. Through this I was able to recognize that research might also be an area that would interest me.

What were the first academic projects you were involved with?

I did a brief bit of work in cancer research when I was a medical student but really the first steps in dementia research were through the Academic Clinical Fellowship that was supervised by Dr Boche and Professor Holmes at the University of Southampton. I worked on postmortem human brain tissue of Alzheimer’s patients and healthy controls who donated their brains for research, looking to see what the effects were of one of the first immunotherapy trials in Alzheimer’s disease (Elan Pharmaceuticals AN-1792). We had access to patient brain tissue from the individuals who enrolled in that trial in 2000. We then looked at the effects of amyloid-beta immunotherapy on brain tissue and found that immunotherapy in established Alzheimer’s disease might accelerate the death of degenerating neurons.

How does your background as a clinician translate into the lab? Does it help or hinder?

A bit of both! I think it helps to be able to take a step back and to see the bigger picture in terms of knowing how to appraise research, how relevant certain areas of research are and to be able to judge how applicable it is to a clinical environment.

However, I definitely am in awe of my lab colleagues. As a clinician I’ve obviously not had as much laboratory experience as them and I think it’s held me back a little bit. It’s taken me quite a lot of time to get up to speed with the techniques and the lab terminology my colleagues use, but it’s great having them around as they’re amazing at what they do, as well as teaching me techniques.

I think working together is a real plus, I can bring another viewpoint on the research and they can give another viewpoint to me. I don’t think you can make too much progress without that collaboration. I think it’s key.

Your research focuses on neuroimmunology and neuroinflammation, what made you choose this area?

I think one of the biggest factors was the number of worldwide experts in neuroinflammation and Alzheimer’s at the University of Southampton. This meant that from early on I was exposed to conversations with people who had done really important work in the field. I think that influenced me a lot.

More than that, it’s a growing area of research with lots of different types of studies; genetic studies, epidemiological studies, postmortem studies, imaging studies, there’s a lot of varied work. I felt that with all these angles it was an area that had a lot of potential in terms of developing better diagnosis rates and new treatments.

What is your current study focusing on?

Currently I am looking at the role of inflammation in dementia with Lewy bodies (DLB) which has a lot of overlap, both clinically and neuropathologically, with Alzheimer’s disease and Parkinson’s disease. There’s lots of research going on in neuroinflammation in Alzheimer’s disease and also quite a lot in Parkinson’s disease, but not very much in DLB.

There have been a few studies with limited patient numbers in DLB, looking at one aspect of inflammation, either in the blood or in the brain, but I’m conducting a study that is looking at both of these areas. This includes a postmortem study comparing inflammation in the brains of individuals who had DLB and healthy controls. I’m also running a cross-sectional observational study looking at inflammation in the blood of individuals with DLB, Alzheimer’s disease and healthy controls. The aim is to get a broad overview of whether the immune system is different in people with DLB.

What is the method behind the research? Are you looking for specific biomarkers?

The first thing we’re doing is checking we have the right patients, so we’re doing immunohistochemistry for diagnostic markers of Alzheimer’s disease and DLB. We’re then also looking at other markers, including microglial markers in the immune system of the brain. For the clinical study we are recruiting patients for thorough clinical assessments. For these patients we are taking blood samples to assess cytokines in the blood and investigating if they correlate with the clinical symptoms of the disease.

What impact do you hope the study will have?

It would be really interesting to see if there is an immune signature in DLB that’s different from Alzheimer’s disease and Parkinson’s disease and from healthy controls. The importance of that would be two-fold; firstly if there is a unique signature you could use biomarkers, either blood-based or imaging brain biomarkers to improve diagnosis rates. Secondly, if you can identify a difference in the immune system in DLB compared to controls, this could open up avenues for new treatments for Parkinson’s and DLB. Certain immune biomarkers are starting to be targeted in Alzheimer’s disease now so the same could apply for DLB.

Why has less research been carried out on neuroinflammation in DLB compared to in Alzheimer’s and Parkinson’s diseases?

Alzheimer’s disease and Parkinson’s disease are much more common than DLB so there’s more money and time invested in those conditions at the moment. Patients with DLB often have delays in diagnosis, more troubling symptoms and carers with increased stress compared to some of these other conditions however, so it’s a really troubling condition. I think we therefore do need to carry out more research in this area.

As to why it’s not happened, apart from the number of people with the condition, I’m not totally sure. It can be hard to recruit people into trials because it is quite a variable condition and patients can vary drastically in terms of how they present so this may have had an impact.

As a clinician where do you feel research within dementia is most needed?

I definitely think that a lot of the money needs to be going into translational research and clinical trials but that can’t really happen until we have a really strong base of scientific knowledge on all the different types of dementia. This means focussing on big areas like neuroinflammation or protein accumulation in the brain.

The other thing that’s really important is improving diagnosis rates. Clinical trials that are running at the moment often have individuals that do not have a confirmed diagnosis and you often don’t find this out until quite a bit later, possibly until after they’ve passed away. Using biomarkers to improve diagnosis rates is a key area, ensuring patients are getting the right diagnosis but also improving the accuracy of clinical trials.

The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Neurology Central or Future Science Group

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