Amyloid and Alzheimer’s disease with Professor Colin Masters
An introduction to the Healthy Brain Project from Dr Rachel Buckley and Dr Yen Ying Lim
We know that sleep can ‘restore’ us, but how might that work at a neural level? Researchers are starting to suggest that sleep allows cellular waste to be cleared and memories to be more deeply em...bedded in our brain. For instance: the volume and flow of cerebrospinal fluid (the fluid washing around your brain and down your spine) increases while you’re asleep, which Ding et al., (2016: Science) are suggesting might facilitate the clearance of Aβ (a hallmark pathology in Alzheimer’s disease). But how does this fluid increase during sleep? The authors measured ion concentrations in waking and sleeping mice via microdialysis, and found that potassium ion levels (used to open ion channels in the brain and keep the brain active) were high during wakefulness, and plunged when mice nodded off. They also found that if they changed the ion concentrations in the brain, they could influence when mice were awake and asleep. Research also suggests that Aβ is most likely cleared during sleep, and that sleep disruption over the lifecourse may precipitate Aβ build up in the brain.
Aβ-amyloid has always had a bad wrap. Scientists have always considered.Aβ-amyloid to be an unfortunate bi-product of a mis-cut protein, which then builds up as an unwanted waste product in the brain (which clump together an...d form plaques). Due to this, Aβ has been the subject of intense research, and recent secondary prevention drug trials (i.e. A4 study). An animal study conducted by Harvard researchers (Kumar et al., 2016: Science Translational Medicine) suggests that Aβ might be a natural antibiotic that protects the brain from infection. In mice models who were engineered to have Aβ in their brain, the protein was found to clump around and ‘imprison’ bacterial pathogens that were introduced into the mouse brain. Perhaps, the authors argue, Aβ plays a protective role in fighting infection? And perhaps Aβ is fighting a falsely perceived infection in Alzheimer’s disease?
In developed countries, mounting evidence suggests that the incidence (i.e. new cases being reported) of dementia is on the decline. Another two findings this year, both on very large datasets (Framingham...: Seshadri et al., 2016: NEJM and Perera et al., 2016: Age & Ageing) are suggesting similarly; there seem to be less new cases, and that the average age of diagnosis is increasing. It is still unclear how this affects less developed countries or whether rates are different in different ethnic groups. Interestingly, rates of dementia diagnoses seem to be higher in females than males.
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Yen Ying Lim, Simon M Laws, Victor L Villemagne, Robert H Pietrzak, Tenielle Porter, David Ames, Christopher Fowler, Stephanie Rainey-Smith, Peter J Snyder, Ralph N Martins, Olivier Salvado, Pierrick Bourgeat, Christopher C Rowe, Colin L Masters & Paul Maruff.
Rachel F Buckley, Paul Maruff, David Ames, Pierrick Bourgeat, Ralph N Martins, Colin L Masters, Stephanie Rainey-Smith, Nicola Lautenschlager, Christopher C Rowe, Greg Savage, Victor L Villemagne & Kathryn A Ellis, on behalf the AIBL Study.
Yen Ying Lim, Paul Maruff, Christine Getter & Peter J Snyder.
Rachel F Buckley, Michael Saling, Kathryn Ellis, Christopher Rowe, Paul Maruff, Lance S Macaulay, Ralph N Martins, Colin L Masters, Greg Savage, Stephanie Rainey-Smith, Alan Rembach & David Ames.
Rachel is a lead investigator of the Healthy Brain Project and an early career research fellow at Harvard Medical School and The Florey Institute of Neuroscience and Mental Health. Her research interests focus on early detection of dementia via subjective concerns of memory decline and determining the reliability of subjective concerns as a risk factor for dementia. Her work is supported by the NHMRC National Institute for Dementia Research, Alzheimer's Australia and the Brain Foundation.
Yen Ying is a lead investigator of Healthy Brain Project and an early career research fellow at The Florey Institue of Neuroscience and Mental Health. Her research interest includes understanding genetic and lifestyle factors that may accelerate or protect against brain diseases. Her work is supported by the NHMRC National Institute for Dementia Research, Alzheimer's Australia, the Yulgilbar Alzheimer’s Research Program, and the Alzheimer’s Association (USA).
Key Senior Mentors
Laureate Professor at the Florey Institute of Neuroscience and Mental Health.
Professor at the Florey Institute of Neuroscience & Mental Health Chief Science Officer, Cogstate Ltd.
Your participation in the Healthy Brain Project can help transform the way that we conduct and communicate our science. At the Healthy Brain Project, we aim to understand how genes may influence risk for developing brain diseases, such as Alzheimer’s disease, depression and post-traumatic stress disorder. By understanding the genetic underpinnings of these diseases, we will obtain important insights into the biological bases of brain disorders, which in turn will provide clues for the development of treatment strategies to slow or even stop disease progression. We are also aiming to understand how risk factors that begin to develop in mid-life (e.g., high cholesterol levels, physical inactivity, diabetes), and protective factors (e.g., social engagement, occupational complexity, diet) act by themselves or together to infer risk for these brain disorders. As these factors are often modifiable, understanding them will mean that we will be able to better inform the types of lifestyle interventions required to help delay disease progression.
We recognise and appreciate the invaluable amount of time and energy that our volunteers have given to the Healthy Brian Project. A key aim of this initiative is to build a community that is interested and invested in learning more about brain health. As such, we encourage all our volunteers to participate in our Healthy Brain Project forum, where you will have the opportunity to discuss recent brain health articles in the media, have your brain health questions answered by one of our experts, support each other in your individual brain health journeys, and be invited to our public lectures, where you will hear about our latest research and meet the brains behind protecting yours. We are also aiming to build a large database of brain health so that we will be able to provide you with some information of how healthy your brain is relative to the general population. At return visits, you will also be able to see how your brain health is tracking over time. Please note that this is NOT a diagnostic service, and we highly recommend that you speak with your primary care physician should you have any concerns about your brain health.
One of the reasons why brain disorders are so hard to cure is because of the length, cost and challenge of conducting clinical trials. The development of a single drug typically takes many, many years. By participating in the Healthy Brain Project, and by completing our surveys and thinking tests, we will be able to better identify individuals who may benefit from being in a clinical trial. This pre-screening process does not only save clinical trials a lot of time, but also allows identified volunteers priority access to brain-health therapeutics. We would like to stress that any information you provide will remain strictly confidential and will only be accessed by the Healthy Brain Project team. Before we provide any information to clinical trials, we will ALWAYS seek your written permission. It is also important to note that if you have been identified for participation in a clinical trial, it DOES NOT mean that you are necessarily at risk of a brain disorder. Many clinical trials require healthy volunteers to act as a basis for comparison. It is as important for us to understand normality as it is for us to understand abnormality.
Basically, our aim is to track a large group of middle-aged Australians so that we can identify which parts of brain biology, genes, psychology and behaviour (or a combination of) can help predict who will progress to a dementia later in life. We will gather lots of data from ~4,000 participants and follow them each year for at least five years (and longer if possible!)
You will be asked to participate in a series of memory and thinking tests, and to fill out surveys related to lifestyle, mood, personality, medical history and demographic information. You can do this over a period of days, whenever you can snatch some spare time! Obviously, we’d like you to do the memory tests in a quiet space, but the surveys can be done on the go on the way to work, if that’s the only time you have!
We will be using your data in a few exciting ways: the first, will be to track your progress over time in relation to your genetic data. In order to fulfil our requirements as researchers, we will be publishing our findings in scientific journals and uploading these publications to the website as we go. Our second way to use your information is to give back information on how you’re progressing in relation to the rest of the group on the website. We are all about open science here! Every time ~500 new participants get involved with the website, we’ll recompute all the averages so that you can determine where you sit in relation to the group. One thing to remember is that our website is NOT a diagnostic service, and is not intended to be used in this way. It is simply our way of giving back to you so that you feel that our work is not a “black box”, but a valuable interaction between scientist and volunteer. Without your involvement, there would be no data!
Your personal information will be kept under lock and key and deidentified. What we mean by that, is that your data will be stored on a secure server at our facility (The Florey Institute of Neurosciences and Mental Health), and all your test scores will be kept entirely separate from your identifying information (i.e. name, email and home address, phone number, etc. We have also performed encryption on your identifying information so that if there were a security breach, your information would not be traceable. We are doing everything in our power to keep your information safe, and are following Australian Medical Record Safety guidelines and are always being monitored and randomly audited by our Human Research Ethics Committees at the Royal Melbourne Hospital. For any concerns or queries, please email us directly at email@example.com
Dr Lim and Dr Buckley are both researchers who are employed by the Florey Institute, and who are honorary affiliated researchers with the University of Melbourne. Our research is monitored and supported by the Florey Institute, and ethically approved by the Royal Melbourne Hospital and the University of Melbourne.
If you have any additional questions or concerns about your participation, please email us at firstname.lastname@example.org or call us at +61 4 7789 0908 or +61 3 9035 3000.