NeuRA Magazine #19



A new way to view a protein associated with cognitive decline in Alzheimer’s disease will be useful for researchers involved in the DIAN study.

tau protein imaging DIAN study

Dr Bill Brooks

Being able to visualise deposits of abnormal proteins in the brains of living people is giving researchers a much better idea of how Alzheimer’s disease begins and progresses. The two hallmarks seen under the microscope in the brains of people who have died with Alzheimer’s disease are neuritic plaques and neurofibrillary tangles. The main component of the plaques is the amyloid-beta peptide (Aβ), whereas the tangles are formed of a protein called tau.

The DIAN study was set up to find biomarkers for Alzheimer’s disease that are detectable before the symptoms begin. Participants are from families where some members inherit the condition as the result of a faulty gene. They undergo brain scans and clinical assessments and provide blood and spinal fluid for research.

Since 2004, amyloid deposits have been detectable in people with Alzheimer’s disease by positron emission tomography (PET) scans of the brain using special radioactive tracers. In the DIAN study, these scans showed that amyloid begins to be deposited in the brain 15-20 years before the age of symptom onset in people with a genetic mutation causing familial Alzheimer’s disease. We believe that amyloid deposition is largely complete by the time people develop symptoms. These results have led to a clinical trial (DIAN-TU-001) of medications to prevent the onset of Alzheimer’s disease in DIAN participants.

Recently, new tracers have been developed to detect tau deposits and neurofibrillary tangles on PET scans. Since the tau deposits are believed to begin much later than the amyloid deposits, and continue during the years when people have symptoms such as memory loss, we expect that tau PET scans will help us to understand the time course and pattern of spread of the Alzheimer’s process in relation to the symptoms experienced by people with the disease.

Tau PET scanning has now been introduced in Sydney for participants in the DIAN-TU clinical trial and is in the process of being introduced for the continuing DIAN observational study.

“This is a major development that will give us the other half of the picture of what happens in the brain during Alzheimer’s disease,” says Dr Bill Brooks. “Tau imaging is at the stage that amyloid imaging was at 10 years ago. As it develops, we will have a much more detailed understanding of how symptoms relate to brain changes. We will also have a new objective marker to monitor the effects of treatments that could potentially delay or prevent the disease process.”

NeuRA is one of 26 sites worldwide participating in the DIAN-TU-001 prevention trial. All of our participants have now completed their first year. An analysis at the end of 2017 will look at the effect of the study drugs on amyloid deposition measured by PET scan and tau levels measured in spinal fluid. Provided that the results are favourable, the study will continue for another two years to see if an effect on preventing memory symptoms can be established.

“Other trials currently in the planning stage will certainly incorporate tau PET imaging as a more immediate measure of effectiveness,” said Dr Brooks.

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Brain and Knee Muscle Weakness Study

Why Does Quadriceps Weakness Persist after Total Knee Replacement? An Exploration of Neurophysiological Mechanisms Total knee replacement is a commonly performed surgery for treating end-staged knee osteoarthritis. Although most people recover well after surgery, weakness of the quadriceps muscles (the front thigh muscles) persists long after the surgery (at least for 12 months), despite intensive physiotherapy and exercise. Quadriceps muscle weakness is known to be associated with more severe pain and greatly affect daily activities. This study aims to investigate the mechanisms underlying weakness of the quadriceps muscles in people with knee osteoarthritis and total knee replacement. We hope to better understand the relationship between the changes of the brain and a loss of quadriceps muscle strength after total knee replacement. The study might be a good fit for you if you: Scheduled to undergo a total knee replacement; The surgery is scheduled within the next 4 weeks; Do not have a previous knee joint replacement in the same knee; Do not have high tibial osteotomy; Do not have neurological disorders, epilepsy, psychiatric conditions, other chronic pain conditions; Do not have metal implants in the skull; Do not have a loss of sensation in the limbs. If you decide to take part you would: Be contacted by the researcher to determine your eligibility for the study Be scheduled for testing if you are eligible and willing to take part in the study Sign the Consent Form when you attend the first testing session Attend 3 testing sessions (approximately 2 hours per session): 1) before total knee replacement, 2) 3 months and 3) 6 months after total knee replacement. The testing will include several non-invasive measures of brain representations of the quadriceps muscles, central pain mechanisms, and motor function and questionnaires. Will I be paid to take part in the research study? You will be reimbursed ($50.00 per session) for travel and parking expenses associated with the research study visits. If you would like more information or are interested in being part of the study, please contact: Name: Dr Wei-Ju Chang Email: Phone: 02 9399 1260 This research is being funded by the Physiotherapy Research Foundation.