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Blood tests could one day be used to tell who is at risk of developing Alzheimer’s disease, say researchers.

Dr Sam Burnham wants to improve our odds of a healthier future. Together with our Preventative Health and Computational Informatics teams, this research statistician is helping us better understand Alzheimer’s disease, the most common form of dementia.

Alzheimer’s disease is the leading cause of dementia and affects 250,000 Australians – a number that is expected to grow to 1 million by 2050. More than 330,000 Australians currently suffer from dementia, and given our ageing population, this is set to triple by 2050. But not on Sam’s watch.

Original Link:

https://blog.csiro.au/the-statistician-on-a-mission/

Using her mathematical wizardry, Sam is working to detect Alzheimer’s at its earliest stages, to give those at risk a better chance of receiving treatment before it’s too late.

The amyloid beta protein in a healthy elderly person (left) compared to an Alzheimer's disease patient (right)

Her team has recently identified blood-based ‘biomarkers’ that are linked to the build up of a toxic protein in the brain called amyloid beta, one of the earliest indicators of Alzheimer’s disease and they recently found it occurs 17 years before dementia symptoms appear.

Biomarkers are natural genes or hormones inside parts of our body like the blood or tissue that indicate early changes in health. They can be anything from body temperature – a biomarker of fever, to blood pressure which determines the risk of stroke.

“We’ve found a panel of nine biomarkers in the blood that can tell us how much amyloid beta is in the brain. This means we can detect the disease years before any dementia symptoms appear. We’re hoping that this will develop into a population screening test.” says Sam.

So what’s maths got to do with it?

“We started off with a few hundred different possible measurements from the blood, and then used sophisticated mathematical models to look at different combinations of these markers, and get down to the panel that we have.”

In the future, these biomarkers could be used in a blood test to make Alzheimer’s detection simpler, earlier and less expensive.

Sam has been investigating biomarkers for Alzheimer’s disease since 2009, when she joined us as an OCE postdoctoral fellow. Before that, she studied Chemical Engineering at Newcastle University in the UK, where she worked on reducing time to market in the pharmaceutical industry, which means putting new medicine on pharmacy shelves quicker.

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Researchers from the Australian Imaging Biomarkers and Lifestyle (AIBL) research group describe the protein Amyloid-Beta (A?) as naturally occurring in the blood and brain. These proteins aggregate to form plaques preceding the onset of Alzheimer’s disease.

AIBL’s Dr Samantha Burnham says this study is the first time the time-course of A? in the onset of  has been quantified statistically.

“There is a general consensus that one of the first things to happen during the onset of Alzheimer’s is the accumulation of this plaque in the brain. However we have never known how long before the onset of disease this happens,” she says.

“Our objective with this study was to say, if we have identified someone who has reached a certain threshold of A? in the , how long do they have before symptoms of dementia occur?”

Burnham and colleagues found seven proteins in the blood samples that, together with a person’s age and cognitive test results, could be used to develop a mathematical formula to predict levels of amyloid in the brain with 80 per cent accuracy.

They validated their findings by showing the formula correctly predicted the level of amyloid protein in the brains of 82 people, from a separate brain scan study.

The researchers are also in the process of fully validating the formula on the other participants in the AIBL study.

At this stage Burnham and colleagues are not sure how the blood markers relate to Alzheimer’s disease.

A patent has been filed by Burnham and two other colleagues covering the blood marker formula and two of the research team members are consultants with Prana Biotechnology.

The researchers used data from the Australian Imaging and Biomarkers Lifestyle Study (AIBL), which is following 11,000 people, aged 60 years and over.

The researchers looked at blood samples from 273 participants who also had brain scans to assess the levels of amyloid protein in the brain.

The study involved 200 , including 36 with early signs of dementia and 19 already diagnosed with Alzheimer’s disease. Participants were assessed every 18 months for almost four years, with neuropsychological examination, MRI, and a PET scan.

At baseline, significantly higher levels of A? were found in patients with AD (Alzheimers) and those with  than in the healthy participants.

“I was tasked with how we could take four year follow-ups from individuals at different stages of the disease and piece them together to give an understanding of what happens throughout the course of the disease,” Dr Burnham says.

“All of those individual four year trajectories had to be complied together to get an overall disease level trajectory.”

During the follow-ups, 82 per cent of participants showed positive rates of A? accumulation, with deposition estimated to take 19.2 years to reach the levels observed in Alzheimer’s disease.

As participants began to show symptoms of AD, the rate of A? deposition slowed towards a plateau.

“There isn’t currently any clear explanation for why the accumulation of amyloid beta occurs or why it aggregates and becomes a solid plaque. We just don’t know at this stage,” Dr Burnham says.

Dr Burnham says the predictions of the rate of preclinical changes and the onset of the clinical phase of AD will facilitate the design and timing of therapeutic interventions aimed at modifying the course of this illness.

“What that means is that we actually have quite a large window for medical interventions to slow the disease,” she says.