About the CoSTREAM project

Project description

Facts and figures

Acronym:	CoSTREAM
Start date:	December 1st, 2015
Duratio:	66 months
End date:	May 31st, 2021
Project coordinator:	Prof. Cornelia van Duijn, Erasmus MC
Consortium:	11 partners - major universities, research institute and industry - from 7 countries
Total funding:	€5,100,372.50
EU contribution:	€4,590,185
Swiss contribution:	€510,187.50

CoSTREAM's context

Stroke is the second leading cause of death, and one of the leading causes of disability worldwide, yet its complex causes are not fully understood. There are 15 million people worldwide who suffer a stroke each year, and although age-standardised rates of stroke mortality have decreased worldwide over the past two decades, the absolute numbers of people who have a stroke, and the overall global burden of stroke increase each year. The number of stroke events in Europe is projected to increase by 1.5 million per year by 2025, largely due to an ageing population. It is estimated that in 2030, 23 million people across the world will have a first-ever stroke.

Stroke will remain the most common cause of dependency in adults worldwide, and European societies are confronted with a subsequent increase in co-morbidities occurring in stroke patients. One of stroke's most important co-morbidities is dementia: within 10 years, 1 in 4 stroke patients develops dementia - in most cases Alzheimer's disease.

The typical Alzheimer's pathology, such as amyloid deposits and neurofibrillary tangles, often occur close to vascular lesions seen in stroke. As Alzheimer's disease is the most common neurodegenerative disease in the elderly, the co-occurrence may be coincidental. However, they co-occur more often than expected by chance. This finding is supported by evidence from epidemiological studies of Alzheimer's disease that have consistently shown that vascular disease, such as stroke, increase the risk for Alzheimer's.

There is an urgent need to better understand the common causes of these two diseases.

Objectives

Our main objective is to understand the mechanisms explaining the co-occurrence of stroke and Alzheimer's.

More specifically, we aim to:

• understand common genetic and molecular signatures;
• identify biomarkers for (co-)morbidities;
• identify evidence-based targets for the development of innovative treatment;
• link and validate these signatures to advanced imaging including MRI and PET;
• discover new compensatory mechanisms that are the basis for discoveries of innovative treatments and preventions based on an in-depth understanding of drivers of pathology and co-morbidity.

We aim to translate these findings into a validated organ-on-chip model of the neurovascular unit for future therapeutic research.

Project output and deliverables

CoSTREAM will develop the following exploitable deliverables, representing significant innovation potential:

• Reports and publications on the commons mechanisms and underlying causes of the stroke and Alzheimer's disease
• A validated platform to determine metabolic biomarkers to predict and monitor the risk of Alzheimer's in stroke patients
  
• Validated neuroimaging markers for monitoring, intervention and prevention
  
• Validated risk factors and compensating factors for better prevention
  
• A validated calculator to assess the risk of Alzheimer's in stroke patients
  
• A validated calculator to monitor the risk of Alzheimer's in individuals at high risk for stroke
  
• A revolutionary organ-on-chip model of the neurovascular unit for therapeutic research

Data and power

We will investigate a combined dataset spanning 11,595 cases of stroke and 19,384 cases of Alzheimer's disease (including mild cognitive impairment) and 74,028 healthy controls with up to 25 years of follow-up, including multiple repeat assessments.

In total more than 250,000 additional samples are available to the project for data mining and analyses via indirect collaborations. We will identify novel ways to prevent AD in clinical stroke patients and asymptomatic older people with preclinical vascular disease based on epidemiological and therapeutic interventions targeting the molecular pathways identified in CoSTREAM.

Impact

We will combine world-class clinical and preclinical research teams to improve the understanding of the pathways that drive the co-occurrence of stroke and Alzheimer's Disease, and will develop a high-throughput platform to characterize these mechanisms to allow intervention targeted on the pathways. The increased knowledge of common mechanisms between both diseases will ultimately lead to less co-morbidity for patients, development of novel evidence-based intervention, better preventive strategies in clinical and public health care, and increased health at an individual as well as societal level.

CoSTREAM will provide a one-of-a-kind easy-to-use prediction toolbox to improving clinical prediction and risk assessment for both stroke and Alzheimer's, and their co-occurence.

Our project fills the urgent need for novel biomarkers, both blood-based and imaging, that aid in the identification of patients with pathology that can be halted to prevent or delay disease. This leads to new directions for clinical research for disease prevention, health promotion, therapy development, and management of comorbidities.

Finally, CoSTREAM will also develop an organ-on-a-chip model for the neurovascular unit, thereby providing an essential tool for the in vitro characterization of pathways underlying both diseases, as well as providing revolutionary opportunities for research on therapeutics.