Imaging as a biomarker for Alzheimer’s disease

Developing a window into the brain for early intervention

By John Beaver
Vice President, Biomarkers

August 1, 2017

I have always been intrigued by the mind/brain connection: how does the biochemistry of the brain affect the mind, the way we think and act and ultimately who we are?

I was first introduced to the biochemistry of the human brain in the 90s while a psychology undergraduate. Back then we knew a lot about the brain chemistry of rodents but surprisingly little about living humans. As I was entering graduate school, medical imaging in humans was beginning to emerge, finally giving us a window into the living brain.  Before imaging, one of the primary ways to study a human brain was post-mortem. This meant that when studying neurodegeneration the brain was typically already severely damaged, giving us only a modest understanding of the disease and its progression. Imaging was going to change all that. I knew then that this technology was going to change the field of neuroscience, finally offering us new insights into the brain and neurodegenerative diseases.

Biomarkers and the brain
Fast-forward 25 years, where science has accumulated an arsenal of tools for imaging the brain. I came to Biogen, a place that invests heavily in brain research and pioneers new potential medicines with a heavy reliance on biomarkers. A biomarker is a characteristic that can be measured as an indicator of a biological process. For example, the measurement of cholesterol levels in the blood is an indicator of cardiovascular health.

I work with a diverse team that brings imaging and other biomarker tools to our drug development programs. We’re a hybrid between applied scientist, computer geek and precision engineer; we identify analytical tools that don’t exist and need to be discovered, or tools that do exist but are immature, and work on the bioanalytics to develop the technologies for application in our clinical trials.

AD diagnosis, disrupted
We are currently trying to identify people with Alzheimer’s disease based on very early physiological changes – in other words, patients who do not yet show symptoms. How can we design biomarkers that are inexpensive, easy to use, broadly deployable and reliable? Our ultimate aim is to disrupt current diagnosis techniques with a means to detect AD in its earliest stages. Similar to the advancement of colonoscopies for early cancer detection, our goal is to develop a routine test that can signal Alzheimer’s very early, to help impace the success of therapeutic intervention.

One area of our focus is to improve the imaging of aggregated amyloid and tau proteins, which form plaques and tangles in the Alzheimer brain. PET scans are an excellent tool for this purpose, but they’re expensive, about 1,500 – 3,000 USD per scan. It’s a chicken-and-egg dilemma: we don’t have a medicine that slows disease progression, so it’s difficult to argue the need for expensive PET scans. Yet without PET imaging, we won’t be able to develop effective medicines.

What we thought we knew, isn’t the whole picture
The maturity of the technology is key. Imaging for amyloid proteins has been used in patients for more than 10 years and is well developed. However, we now know that the amount of amyloid plaque does not appear to be related to Alzheimer’s symptoms. It builds up earlier and patients can have a substantial amount of plaque with no or only mild dementia symptoms. Tau related tangles, on the other hand, seem to correlate better to Alzheimer’s symptoms. As tau spreads from neuron to neuron, dementia progresses.

We want to know if there’s an interplay between the amyloid and tau aggregates and the severity of the disease. Imaging techniques for tau neurofibrillary tangles is still immature, so we’re partnering with Merck and Cerveau to co-develop an imaging agent to observe tau protein deposits in patients’ brains.    

We plan to research both amyloid and tau imaging agents in parallel to confirm the onset of Alzheimer’s disease and compare the effect of experimental interventions over time. The challenge is to properly interpret and quantify the biological meaning of these measurements. Then, working backwards from our findings, we may, one day, be able to rely on these imaging methods to predict the onset of Alzheimer’s disease.

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