Alzheimer’s researcher goes back in time to move forward in diagnosis

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Shawn Whitehead will be doing some medical time traveling as he works to pinpoint the roots of cognitive impairment, including Alzheimer’s disease.

“A lot of the biomarkers that are currently part of the Alzheimer’s world don’t necessarily predict future risks,” said the Schulich Medicine & Dentistry professor. “By the time a patient is diagnosed, at that point treatment options are very limited. We’re trying to turn the clock back 20 to 30 years and see if we can detect blood-based biomarkers that could predict risk, not only of Alzheimer’s, but also vascular dementia or other forms of cognitive impairment.”

Whitehead, BSc’00 (Physiology), PhD’05, was recently awarded an Alzheimer Foundation London and Middlesex Premier Research Grant 2020 ($100,000 over two years) to study brain inflammation as a potential predictor of cognitive impairment.

Brain inflammation, due to the chronic activation of what is called microglia – which accounts for 10-15 per cent of the cells found in the brain – is a significant contributor to Alzheimer’s disease pathology, said Whitehead.

The classical biomarker physicians use is a cerebrospinal fluidanalysis – also known as a spinal tap – but it is more a diagnostic tool than a predictor.

Outside of costly, invasive, limiting imaging techniques, such as PET or MRI scans, there is currently no method to measure this triggering.

However, microparticles released from the microglia cells into the body can be used as an indicator of specific inflammatory processes occurring in the brain, said Whitehead. That’s why developing a blood-based biomarker could help predict and diagnose cognitive decline.

“The body releases microparticles and in these are proteins we can trace back to the individual cell that released them, in this case specifically from the brain,” he said. “One of things we know is brain inflammation is one of the earliest detectable features that are going to predict cognitive impairment. We know with white matter, which is the main connecting component of the brain, that inflammation occurs decades prior to diagnosis.

“What we don’t know is how are you going to detect this in a patient, unless they get an MRI? But are you going to put everyone in an MRI? That isn’t feasible. This would simply be a blood draw instead of spinal tap or MRI.”

Because white matter pathology begins in midlife, and occurs prior to Alzheimer’s disease symptoms, methods aimed at detecting early pathological changes during this critical timeframe must be developed, said Whitehead.

Hypertension, diabetes and obesity significantly increase risks for cognitive impairment, he added, so if these individuals can be targeted much earlier in life – say, in someone’s 40s and 50s – preventive therapies could begin decades before cognitive impairments would begin.

Whitehead, who heads up the Vulnerable Brain Lab at Western, is working with PhD student Austyn Roseborough and Schulich Medicine & Dentistry professor Steve Pasternak, who has developed the microparticle detection system.

“The take home with this is the predictive biomarker for all, which is really needed,” said Whitehead. “We’re in the early stages of this development. I call it the first heat of a marathon. This is very promising, though, as it has shown targeting early to mid-life is critical. Identifying people at risk is the first step, finding out how you’re going to do that is the second step. We just have to keep plugging away at it.”