Organ-on-a-chip model helps explore underlying pathways shared by stroke and dementia

Reviewed by Alina Shrourou, B.Sc. (Editor)Oct 29 2018

Stroke is the second main cause of death globally, and a major cause of disability. Around 15 million people worldwide suffer a stroke each year, and rates are climbing, with the number of strokes in Europe set to increase by 1.5 million per year by 2025 – due in large part to the aging population. Meanwhile, Alzheimer’s disease is the most common cause of dementia and is rapidly developing into the most costly disorder in the EU, negatively impacting the life and well-being not only of the patients but also the relatives and society at large.

It is well established that stroke and Alzheimer’s disease often occur together and can develop in parallel. Within a decade of experiencing a stroke, a quarter of patients develop dementia – most commonly, Alzheimer’s.

Similarly, patients with Alzheimer’s often exhibit high-risk factors for stroke. But with the underlying molecular mechanisms behind the development of both diseases unclear, there is an urgent need to better understand their common causes.

To tackle this challenge, the EU-funded COSTREAM project has brought together a consortium of geneticists, epidemiologists, radiologists and neurologists in a huge undertaking, part of which involves studying data from 12 000 cases of stroke, 20 000 cases of Alzheimer’s, and 74 000 healthy people in conjunction with 25 years of follow-up research. The researchers hope that their work will revolutionize drug development for these widespread and devastating diseases.

‘Our ultimate aim is to understand what causes stroke and Alzheimer’s disease and discover the genetic, metabolic and environmental pathways that are common to both,’ explains project coordinator Cornelia van Duijn of Erasmus University Medical Center in the Netherlands. ‘The mission of COSTREAM is to develop targeted and precise early treatment and preventive strategies.’

Organ-on-a-chip

With work under way since 2015, members in the consortium have combined their vast expertise on the genetics of both stroke and Alzheimer’s and used the data available world-wide to make a comprehensive atlas of the genes driving the disorders. These include those directly related to the diseases themselves or indirectly through established factors such as dysfunction in lipid or immune pathways.

The team has also looked into identifying new biological pointers for stroke and Alzheimer’s using state-of-the-art metabolomics (the large-scale study of small molecules or metabolites). Data collection has already revealed metabolites that are determining both disorders. The plan is to link these metabolites to genetic and environmental factors already observed in the groups being studied and validate biomarkers from blood in relation to the current understanding of the diseases using modern brain-imaging techniques.

In parallel, the team is working on an ‘organ-on-a-chip’ lab model that can replicate the blood-brain barrier – the place where blood vessels connect to brain cells – on a tiny scale. This model is helping to characterize and validate the underlying pathways shared by the two diseases and could revolutionize the development of new therapies against them by allowing quick, efficient testing.

These developments will allow COSTREAM to develop a ‘prediction toolbox for stroke and Alzheimer’s disease’ which can then be used to direct possible therapies and approaches for monitoring disease progression that can be tested in the organ-on-a-chip model.

In the future, it is likely that stroke patients will give a blood sample and undergo a brain scan that will identify their risk of developing dementia.

Bigger than big data

Now halfway through the project, the COSTREAM team has successfully integrated the data generated by the epidemiological and clinical follow-up studies to determine the overlap in the genetic and metabolic drivers of Alzheimer’s disease and stroke.

‘The main challenges are to capture the interplay between genetic and environmental risk factors – we need bigger than “big data” to do this,’ says van Duijn.

This is an ambitious project, with many barriers still to be overcome but work is on track and this team is positive they can make it happen.