The ADAIR project is funded under the 2019 JPCO-Fund call for Personalised Medicine under the grant number, JPND2019-466-037 . ADAIR is funded from 2019 to 2022.
Despite decades of Alzheimer’s disease (AD) research, the real molecular pathophysiology of the diseaseis still poorly understood, and treatmentsremain inadequate. Remarkably little attention is paid to the involvement of environmental factors, which areknown from epidemiological studies to strongly impact AD generation1. Furthermore, even though the majorityof patients suffer from sporadic, or early-onset AD (LOAD), most preclinical research is carried out using genetic models, or studies focus solely on genetic risk factors. To truly advance the fieldand match the right patients to right therapies, it is important to (i) focus studies to LOAD, (ii) use clinically relevant research models, (iiI) account for the exposure environment of individualsin cohort studies, and (iv) stratify individuals into subgroups for efficient diagnosis, disease riskassessment,and tailoredtreatment.
Air pollution, a massive public health issue known to pose a major threat to human health, is an important, ever-increasing global concern. Every year, 7 million premature deaths from cardiovascular and respiratory conditions occur as a direct result of exposure to air pollutants, especially to particulate matter (PM). A growing body of experimental prooffrom epidemiological studies and controlled animal studies shows that exposure to air pollutants also impairs the brain. Living in highly polluted areas is associated exacerbated cognitive dysfunction and AD. Yet many questions remain unanswered as mechanistic information onair pollutant effects in brain is scarce. Importantly, biomarkers for air pollution and AD risk prediction do not currently exist, thus hindering the identification and stratification of individuals at risk for harmful air pollution effects.
Summary of ADAIR Research
Aims of the Project
ADAIR applies a precision medicine approach to stratify individuals to subgroups for risk estimation and future AD prevention, ultimately aiming to target air pollution induced effects in those individualsthat can most benefit from them. The project investigates the novel, ambitious hypothesis that the pollutant exposure environment of an individual alters cellular mechanisms and functions, resulting in the expression of measurable biomarkers. By identifying biomarkers, the individuals with increased AD risk can be stratified prior to the disease onset and preventive measures can be targeted to the specific at-risk populations in order to be most effective.
The main objectives are to:
- Discover biomarkers of air pollutant effects. Correlate biomarkers to AD risk to identify sub-groups of individuals with an increased susceptibility for air pollutant effects.
- Better understand how the exposure environment is linked with complex disease mechanisms underlying AD, thus paving the way for future therapeutic approaches.
The specific aims are to:
- Identify biomarkers of acute air pollution exposurein humans using high-throughput omics.
- Correlate expression of the identified biomarkers in acute exposures to long-term pollutant exposure in samples from the Betula and Rotterdam studies using novel data integration tools.
- Determine the value of the biomarkers for AD risk evaluation by measuring the biomarkers during the clinical course of AD in people living in low vs. high polluted areas.
- Discover how air pollutant exposure results in cellular dysfunction by assessing both functional alterations and cellular mechanisms induced.
- Assess whether air pollution exposure status can be used to identify sub-groups of individuals at high risk of developing AD.
- Provide important information for preventive interventions with regards air pollution exposure and AD risk that can be used for indicating prevention potential in individuals.
Impact of the Project
ADAIR address a major societal challenge with wide health-related, environmental, economic, scientific, social, and political impact. Lowering the burdenof AD attributable to air pollution and contribution to the mitigation of climate change, are closely linked.The ultimate goal is to develop strategies for early identification of people at risk of AD, and to discover novel targets for preventive strategies to reduce the health care and socio-economic burden of AD. ADAIRdevelopstools for riskassessmentand forpreventative measures, eg. byidentification oftheindividuals most likely tobenefit from intervention.ADAIR will result in newIP to form the basis for new products and services.
The fact that we will use biological samples and data from LOAD patients will provide new insight into the factors involvedin this most common disease form and may lower the translational barrier between basic research and clinicsleading to economic benefit to health care through the ability to target future therapies to those who can most benefit from them.
Efficient dissemination and communicationensure maximal impact for both scientific and regulatory purposes. The outcomes of ADAIR guidepolitical decision making for efficient reduction of air pollutants, which could reduce the economic burden caused by not only AD, but other brain diseases of the brain, lungs and cardiovasculature.Sinceair quality is closely linked to the earth’s climate, policies aiming to reduce air pollutionalsocontribute to the mitigation of climate change.