Biomarkers for mixed neurodegenerative pathologies
Discovering blood-based biomarkers for Lewy body disease, TDP-43 pathology, and other non-AD proteinopathies.
The problem
What's the challenge, and why is it so hard to solve?
Many individuals with dementia have multiple brain pathologies, including Alzheimer's disease, Lewy body disease, and TDP-43 proteinopathy. While blood-based biomarkers for Alzheimer's disease have advanced rapidly, reliable biomarkers for other common neurodegenerative pathologies remain limited. This gap makes it difficult to identify mixed pathologies during life, accurately diagnose patients, and select appropriate therapies.
Our approach
How are we tackling the challenge?
We use immunoprecipitation-mass spectrometry (IP-MS), proteomics, and aggregate seeding technologies to discover and develop biomarkers for Lewy body disease, TDP-43 proteinopathy, and other non-Alzheimer's neurodegenerative pathologies. Through IP-MS, we characterize disease-specific protein forms, including pathological post-translational modifications, cleavage products, and novel biomarker candidates. In parallel, we are developing blood-based aggregate seeding assays that provide functional readouts of protein aggregation and propagation.
Why it matters
What difference could this make for patients and society?
A detailed understanding of the specific pathologies present in each individual is essential for precision medicine in neurodegenerative disease. Biomarkers that detect Lewy body disease, TDP-43 proteinopathy, and other mixed pathologies could enable more accurate biological classification, improve patient selection for clinical trials, and facilitate the development of pathology-specific therapies.
What's next
Once we've solved this, what do we want to explore next?
Next, we want to leverage clinically characterized cohorts of non-AD and mixed dementias, together with autopsy-confirmed cohorts, to discover and validate biomarkers that detect multiple co-occurring pathologies, rather than one pathology at a time. Promising candidates will be translated into scalable blood-based assays for research and clinical applications.
Key publications
Where can I read more?
Team
Who's working on this?