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Optimizing stratification for trial design in Alzheimer’s disease

Project description

Improving Alzheimer’s trial designs for better treatments

Alzheimer’s disease (AD) does not follow a single path. Its progression varies widely among individuals due to differences in risk factors, symptoms and cognitive decline rates. Despite this, clinical trials often take a one-size-fits-all approach, which limits their success in developing effective treatments. As researchers focus on earlier interventions, refining trial design is essential to improving outcomes. A key challenge is identifying subgroups of patients who may respond differently to treatments. With the support of the Marie Skłodowska-Curie Actions programme, the STRATA-ALZ project tackles this issue by analysing neurobiological differences in over 2 900 individuals from different cohorts. By identifying distinct AD subtypes and assessing disease progression factors, the project aims to create data-driven guidelines, ultimately increasing the likelihood of successful therapies.

Objective

Alzheimer’s disease (AD) heterogeneity is associated with distinct risk factors, clinical manifestations, rates of cognitive decline, and comorbidities. However, this population variance is not properly incorporated in clinical trial design, directly hampering successful development of treatments. As the field is shifting towards (early) secondary or event primary intervention, the overall objective of the current project is to optimize clinical trial design of an early AD population, by providing data-driven guidelines for sample stratification and outcome measures. To this end, I will assess neurobiological heterogeneity in ~2000 cognitively unimpaired (CU) and ~900 mildly impaired (MCI) subjects enrolled in the BioFINDER study from Lund University (host institution). Using their unique data-set, I aim to identify subtypes of amyloid-β (Aβ)-vascular interplay, the two most common co-occurring and interacting pathologies in the aging brain. Next, the role of neuronal function, microglial activation, and novel targets through proteomics analyses based on CSF/plasma biomarkers on disease progression within these subgroups will be determined. Finally, resulting tau-PET accumulation patterns and cognitive decline across domains across will be assessed. A main innovative aspect and strength of this project is the utilization of regional information available from the imaging modalities, an aspect of analyses which I have specialized in. In turn, the expertise of the host institution regarding fluid biomarkers and tau-PET imaging is paramount to support this multi-modal project. Finally, our respective experience with longitudinal study design will support a critical aspect of the project, which is lacking even in the most comprehensive studies to date. Unravelling heterogeneity in disease trajectories is paramount to optimize trial population selection and stratification, directly increasing the changes of positive trial outcomes.

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

LUNDS UNIVERSITET
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 206 887,68
Address
Paradisgatan 5c
22100 Lund
Sweden

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Region
Södra Sverige Sydsverige Skåne län
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

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