Analysis of extracellular vesicle cargo as biomarkers to differentiate Alzheimer’s disease and dementia with Lewy bodies

Summary

Extracellular vesicles (EVs) are tiny structures which are released by cells in the body. By analyzing the contents of neural-derived EVs (NDEVs) released by brain cells, we hope to better understand and track the changes that occur in the brain during diseases like Alzheimer’s and dementia with Lewy bodies.

What are we doing?

The diagnostic tools currently available surrounding dementias such as Alzheimer’s disease (AD) and Lewy body dementia (LBD) are limited. Current tests include neuroimaging and the analysis of cerebrospinal fluid (CSF), which are both expensive and invasive. Added to this, the neuropathology shown during the course of AD and LBD show considerable overlap, complicating the diagnostic process. This means that at times a concrete diagnosis may not be possible until post-mortem analysis. Identifying novel biomarkers is crucial to move towards early diagnosis and personalised care for dementia patients.

NDEVs provide promise. The way that EVs are created means they contain various cargos (proteins, lipids, and genetic material) from the original cell. The ability to collect EVs originating from neurons in the brain (NDEVs) offers us a unique opportunity to indirectly measure pathology in these cells. What is more, NDEVs can be isolated from blood, offering a non-invasive alternative to current tests.

How are we doing it?

Our aims are to:

• assess differences in cargo exhibited among NDEVs from AD and LBD patients, allowing us to establish disease-specific NDEV profiles for diagnostic purposes
• measure NDEV cargo exhibited during early stages of disease – among individuals with mild cognitive impairment (MCI) – and to therefore assess these markers as early diagnostic tools
• assess the stability of NDEV biomarkers over time

Individuals from four different groups – AD, LBD, MCI, and healthy controls – will provide blood samples at two time points (the original appointment, and after 3 months). Blood will be processed to platelet-free plasma, from which NDEVs will be isolated using established methodology. Following this, proteins known to be associated with neuropathology (amyloid, tau and α-synuclein) during both AD and LBD will be quantified and compared between groups.

What happens next?

We’d like to build on this research by conducting transcriptomic analysis on similar samples – looking at how genetic changes observed in NDEVs reflect those associated with disease. We’ll also start to compare NDEV biomarkers to those currently available, such as plasma/whole blood markers, CSF markers, and imaging approaches.

Collaborators

Professor Jon Brown, University of Exeter

Professor Nick Ashton, University of Gothenburg

Dr Esra Bozbas, University of Exeter