EPND project researchers shed light on the biological heterogeneity of Alzheimer’s disease

Currently, there is no treatment that prevents or modifies the progression of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. In Europe these conditions affect millions of people. The discovery of biomarkers detecting the early onset of neurodegenerative diseases is a necessary step towards the development of effective treatments. These biomarkers aid with the assessment of treatment efficacy and patient stratification. 

To this end, the European Platform for Neurodegenerative Diseases (EPND), an Innovative Medicines Initiative (IMI) – funded public-private partnership, integrates existing European initiatives to build an infrastructure that facilitates access to biological samples and data in order to accelerate biomarker discovery and validation and potentially aid the development of therapeutics for neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease.

The findings

The underlying physiology of Alzheimer’s disease in particular is very diverse and this is thought to be one of the reasons for the limited success of Alzheimer’s drug trials. At the start of 2024, EPND partners from Amsterdam UMC and Maastricht University successfully identified five molecular subtypes of Alzheimer’s disease. The findings are based on biomarker analyses of cerebrospinal fluid samples collected from 419 Alzheimer’s patients, and compared to 187 healthy people, as a control. 

“There’s more than 140 drug targets that are being studied for Alzheimer’s disease and we can see indications in our data that a particular target might only work for a subgroup of patients,” says Betty Tijms (Maastricht Universtity), who is the lead author of the published results. “Clinical trials are testing the same drug on all of the Alzheimer’s patients without considering those subgroups and so if it only works for one subgroup and not for the others, then it is more difficult to see treatment effects. Now we know the subgroups exist, we can test for this.” 

The study participants were selected from cohorts available in the EPND Catalogue. “It’s not easy to collect cerebrospinal fluid samples from so many people, all with different diseases”- adds Tijms. “You need very large, high-quality patient samples – such as those found in the EPND catalogue.” These findings illustrate the importance of sharing bio samples and data to find meaningful patterns in biological data, potentially aiding in the development of tailored treatment to optimise patient outcomes.

Read the published results in the article, here.

Next steps

Moving forward, EPND researchers hope to be able to find similar subtypes in Parkinson’s disease and dementia with Lewy bodies where data are much sparser. “We’re going to repeat this discovery exercise,” says Tijms. “Now we don’t know whether there are subtypes in Parkinson’s and we don’t have any tools to identify them. This is where EPND is at the frontier - we are able to find those groups that are large enough to start this subtyping."

Lygature in EPND

Lygature was involved in the set-up phase of EPND, and provides partnership management and communication support, aids in stakeholder engagement, and brings regulatory expertise to the project.

Program management

Together with Gates Ventures, Lygature coordinates and manages this multi-stakeholder program on a day-to-day basis. Among others, Lygature is responsible for facilitating internal communication and information distribution within the consortium. Moreover, Lygature ensures transparency, stimulates collaboration between partners and monitors the effective execution of the work plan and its progress. 

Stakeholder engagement 

Lygature assists in the development and deployment of effective stakeholder engagement. Through Delphi rounds, Lygature identifies and prioritizes needs, requests and expectations of different stakeholders relative to active engagement within EPND. This helps clarify the scope and modality of stakeholder collaboration, how contributions are used within EPND, and the benefit to stakeholders. 

External communication and dissemination

Lygature supports the development and implementation of the Communication and Dissemination plan for EPND. The project makes use of multimedia approaches to disseminate information on EPND to its target audiences - the scientific community, healthcare professionals, industry, regulators, policymakers, patients and the general public. 

Regulatory expertise

Lygature co-leads the consultations with Expert Advisory Groups for EPND. Lygature co-organises multi-stakeholder workshops, round-table interviews and Delphi surveys to address topics of particular relevance and to gain insights and input from a broad range of stakeholders (both within the EU and beyond) on key project developments. Importantly, in order to increase the impact of EPND on the regulatory validation of biomarkers/diagnostics, scientific advices, opinions and reviews issued by the European Medicines Agency and other regulatory authorities (e.g. FDA) will be scrutinized for a number of questions related to biomarker validation, including quality of the data and principles related to sharing and access of data and samples.