Twelve international research teams are competing for £1.5 million in finance from the Dementia Frontiers Fund after being awarded seed funding to accelerate their boldest ideas.
Launched by Gates Ventures and Alzheimer’s Research UK, the Dementia Frontiers Fund will push the boundaries of dementia research. It unites research teams from different disciplines and countries to take on the field’s toughest unanswered questions. This collaborative approach creates space for ambitious science that could transform how we understand, diagnose and treat dementia.
The response to the initial challenge, launched last October, has been extraordinary: 132 teams from 29 countries across the globe submitted their ambitious ideas. From that stand-out response, these 12 teams have now been selected to pitch to leading experts in the field this summer.
Dr Niranjan Bose, Managing Director for Health and Life Sciences at Gates Ventures, said:
“The strength of response we’ve seen so far shows just how much momentum there is in the global research community, and why it is so important to create space for bold ideas that could genuinely move the field forward.”
Dr Susan Kohlhaas, Executive Director of Research and Partnerships at Alzheimer’s Research UK, said:
“What is exciting about the teams selected is the breadth of expertise they bring together in their ambition to tackle some of the toughest questions in dementia research. They have real potential to push the field forward in important new directions.”
The global programme is supported by research partners the Robertson Foundation and the Alzheimer’s Disease Data Initiative, and made possible by Q Charitable Trust.
Together, these teams are taking on three critical questions that could transform how dementia is understood, diagnosed and treated.
MEET THE TEAMS
Question 1: Can we better predict and stage disease progression in dementia?
We still do not know enough about when dementia symptoms begin, how quickly they will progress, or why people with similar biology can experience very different disease trajectories. Answering this question will improve our ability to stage disease and forecast how dementia progresses in different individuals. Better prediction tools would enable earlier, more targeted interventions and improve the design and interpretation of clinical trials.
Mayo Clinic Study of Aging Platform: Predicting Absolute Risk of Cognitive Impairment in Multiple Populations
Led by Professor Clifford Jack Jr and Professor Ronald Petersen (Mayo Clinic), this work brings together researchers from the US, Australia and Spain.
They aim to enrich and extend analyses across 4 major longitudinal and diverse cohorts to create a uniquely rich data set that will aid in developing next-generation prediction models. This proposal directly addresses the need for multi-marker prediction tools and aims to produce a generalisable absolute/lifetime risk score for Alzheimer’s disease (AD) to enable earlier detection and thus earlier intervention of the disease.
Scalable multimodal AI system for early detection and staging of cognitive impairment
Led by Professor Vijaya B. Kolachalama and Professor Rhoda Au (Boston University), this work brings together researchers from the US, Malaysia, Pakistan, France, and UK.
This team will develop and release open-source and scalable AI pipelines that can rapidly harmonize disparate dementia datasets from LMICs and the United States. This will deliver a more globally diverse integrated dementia resource; validated tools for earlier detection; frameworks for clinical trials with reduced geographic and income bias; and predictive models for long-term patient and family outcomes.
Decoding the Biological Terrain of Alzheimer’s Progression: Integrating Co-Pathology, Omics, and Systemic Drivers
Led by Professor Duygu Tosun (University of California San Francisco) and Dr Oliver Robinson (Imperial College London), this work brings together researchers from the US, UK and Spain.
This proposal will focus on the critical amyloid-to-tau interval that is closely tied to clinical decline to determine the accelerants and retardants of symptom onset. This proposal takes a targeted approach through leveraging several longitudinal datasets with incorporated co-pathologies to address specific mechanistic questions that could reveal early predictors of symptom onset and guide preventative interventions.
Question 2: Why are some high-risk populations resilient to dementia?
Some individuals remain cognitively healthy despite risk factors or even significant brain pathology. Answering this question will uncover the biological mechanisms that underpin this resilience and translate them into new strategies for prevention and treatment of dementia. A deeper understanding of resilience will open up entirely new avenues for preserving brain health and delaying or preventing disease.
Elucidating the synaptic basis of cognitive resilience to Alzheimer’s disease in humans
Led by Dr Patricio Opazo (University of Edinburgh) this work brings together researchers from the UK
This team aims to identify the synaptic basis of cognitive resilience to Alzheimer’s disease in humans through a multi-modal approach, combining molecular profiling of synapses from resilient individuals with target validation in human neurons. This proposal has the potential to inform new therapeutic strategies that harness the brain’s intrinsic ability to preserve synaptic integrity and sustain cognitive function.
A Roadmap to Alzheimer’s Resilience: Defining, testing and shifting resilience across people and cells
Led by Professor Zameel Cader (University of Oxford) and Professor Tony Wyss-Coray (Stanford University), this work brings together researchers from the UK, US and Korea
This team will investigate the influence of gene-environment contributions and drug modulation on resilience to Alzheimer’s Disease. By testing resilience signatures in human iPSC systems and people, and exploring pathways for pharmacological enhancement, there is possibility for insights into new brain resilience therapies and treatments.
EMERALD: Epigenomic Mechanisms of Extreme Resilience and APOE Liability in Dementia
Led by Dr Sarah Marzi (King’s College London), Associate Professor Henne Holstege (Vrije Universiteit Amsterdam) and Dr Alexi Nott (Imperial College London), this work brings together researchers from the Netherlands and the UK
This proposal will characterise cell-type-specific epigenetic signatures of cognitive resilience, contributing a foundational resource for therapeutic target discovery as part of the human atlas of cognitive resilience within the Brain Resilience Hub. The team will leverage the 100-plus study of Dutch centenarians, a uniquely resilient population, and integrate in vivo, pre-mortem, and post-mortem gene regulatory and omics data to produce a multidimensional pipeline to discover potential resilience interventions.
Autoantibody-mediated cognitive resilience in Alzheimer’s disease
Led by Professor Lahiru Handunnetthi (University of Oxford), this work brings together researchers from the UK
This team aims to uncover how autoantibodies contribute to cognitive resilience. They will combine human stem cell-derived neuronal models with proteomics to identify and characterise autoantibodies and their neuronal targets directly from patient samples. The team highlights autoantibodies as promising biomarkers of resilience and emphasises the strong translational potential of identifying protective antibody targets. This work could open new avenues for immune-based strategies to promote cognitive resilience.
Leveraging sex biology and endocrine aging to identify novel contributors of resilience to neurodegeneration and dementia
Led by Associate Professor Jennifer Rabin (Sunnybrook Research Institute and University of Toronto), based in Canada
This proposal will focus on cognitive resilience through a sex-informed, endocrine-focused lens, investigating how mid-life hormonal changes may influence resilience in later life. By integrating deep multimodal phenotyping and leveraging existing biomarker and ageing-study infrastructure, the proposal aims to generate valuable mechanistic insights into an understudied area in dementia research.
Question 3: What are the relative contributions of different brain pathologies to the development of dementia?
Dementia often involves multiple co-occurring pathologies. Answering this will untangle their individual contributions and how they interact to drive disease onset and progression, helping to pave the way for precision medicine and combination therapies that target multiple mechanisms rather than focusing on a single pathway.
Dissecting dementia co-pathologies: genetic and molecular determinants
Led by Dr Petroula Proitsi (Queen Mary University of London), Dr Cristina Legido-Quigley (King’s College London), and Dr Laura Winchester (University of Oxford), this work brings together researchers from the UK, US and Australia
This team aims to define the genetic and molecular signatures associated with dementia co-pathologies. To achieve this, they will leverage multiple post-mortem cohorts, some of which have paired antemortem blood samples and build a large-scale integrated database. By developing a co-pathology stratification framework, this work has the potential to improve patient stratification, inform multi-target therapeutic strategies, and ultimately increase the likelihood of clinical success.
Understanding co-pathologies in Alzheimer’s disease to enable improved molecular diagnosis and precision therapies
Led by Professor Pietro Fratta and Professor Selina Wray (University College London), this work brings together researchers from the UK and the US
This team will focus on TDP-43 and α-synuclein pathology, their influence on core AD processes and how they shape innate and adaptive immune responses. The proposal adopts an integrated mechanistic framework that links post-mortem pathology, experimental modelling and biomarker development that altogether could enhance diagnostic and prognostic accuracy.
Mapping genomic hotspots of neuronal and glial somatic mutations in Alzheimer’s disease at single molecule resolution
Led by Dr Sourena Soheili-Nezhad (Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Centre), Professor Floris Foijer (European Institute for the Biology of Ageing), and Professor Christos Proukakis (University College London), this work brings together researchers from the Netherlands, UK and US
This proposal aims to generate a high-resolution genomic map of somatic mutations and identify genomic ‘hotspots’ of mutation that may drive AD. Detecting these ‘hotspots’ could provide new entry points for mechanistic disease models and allow tailored therapeutic approaches for patients.
Multi-modal nanoscopic and molecular mapping and modelling of human neurodegenerative disease progression
Led by Dr Annelies Quaegebeur (University of Cambridge), this work brings together researchers in the UK
This team aims to establish a mechanistic multi-modal framework for tracking disease progression through advanced microscopy of protein aggregates, synapses and molecular signatures. The resulting models could provide a biological foundation for a clinically interpretable framework to improve the understanding of disease heterogeneity and enabling more precise alignment between underlying pathology and therapeutic strategies.
What happens next
Over the next three months, the 12 teams will work to turn these bold ideas into high-impact proposals, as well as deepen their international collaborations, and sharpen plans for the next phase.
Later this summer, the teams will pitch to the Fund’s expert panel for the chance to progress within the Dementia Frontiers Fund.
We can’t wait to see how these teams build on this momentum to open up new frontiers in dementia research, and bring us closer to better outcomes for everyone affected by dementia.
