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Picture of the article on Ilana Caro and the new biological fingerprint of cerebral small vessel disease
Ilana CARO © Gautier DUFAU

A young researcher within the ELEANOR team of Bordeaux Population Health, Inserm U1219, led by Dr David-Alexandre Tregouët, a member of the VBHI executive committee, and working closely with Prof Stéphanie Debette, the institute’s omics lead in charge of the VBHI – Translational Omics Centre programme, Ilana Caro has just published a study on the proteogenomics of cerebrospinal fluid and plasma, revealing a new biological signature of cerebral small vessel disease. Interview.

What’s your background?

After completing a Master’s degree in Genetics, Genomics and Systems Biology at the University of Nantes, I continued my training within the ELEANOR team at the Bordeaux Population Health Research Center. I first worked under the supervision of Dr. David-Alexandre Trégouët during my Master’s internship, which focused on extending a miRNA alignment pipeline to other small non-coding RNAs.

I then pursued my PhD under the supervision of Prof. Stéphanie Debette as part of the RHU SHIVA project, aiming to characterize the molecular mechanisms of cerebral small vessel disease using multi-omics approaches.

I am now continuing my work as a postdoctoral researcher with Prof. Stéphanie Debette, mainly studying the proteomic and epigenomic aspects of cerebral small vessel disease.

*Omics encompass a set of disciplines that study all the components of a biological system, such as a cell, a tissue or an organism. Instead of analysing a single gene or a single protein, they examine the entire network of components to understand how they function and interact. Multi-omics data are generated by analysing several omics layers, such as genomics, metabolomics, transcriptomics and proteomics.

What did you investigate in this scientific publication?

Our work focuses on cerebral small vessel disease. This is a complex condition, very common in the general population but still poorly understood, which contributes to many strokes and cognitive disorders, particularly in older adults.

It can be detected years before the onset of clinical symptoms, notably through brain imaging (MRI).

In this study, we examined proteins and associated genetic variants (proteogenomics) measured in the cerebrospinal fluid and blood, and their associations with MRI markers of cerebral small vessel disease, to identify biomarkers and better understand the underlying mechanisms of the condition.

The goal is to gain a detailed understanding of the pathways involved in the deterioration of small blood vessels in the brain and the resulting increased risk of stroke and dementia.

Why are you interested in this subject?

We are interested in this topic because cerebral small vessel disease is a major public health issue: it affects a large number of people but is often diagnosed late.

By identifying earlier and more precise biomarkers, we hope to pave the way for better prevention and more timely diagnosis.

Why is this a major discovery?

This is an important discovery because, until now, we have lacked reliable biomarkers to study and diagnose this disease.

Our approach combines, for the first time at this scale, proteomics and genomics in the two most informative fluids for the brain:

  • cerebrospinal fluid and
  • plasma.

This integrated analysis allows us to highlight key biological pathways, notably those related to inflammation, already from early adulthood (~20 years old), and extracellular matrix dysfunction.

Our work also enables the identification of proteins associated with the risk of stroke and dementia, and highlights potential opportunities for drug repurposing for cerebral small vessel disease and its clinical consequences.

These findings therefore provide a true molecular fingerprint of the disease, which could transform the way it is detected, monitored over time, and even how future treatments are developed.

What is the next step?

The next step is to validate these biomarkers in larger, longitudinal cohorts. This will allow us to determine whether they can predict the onset or progression of the disease.

We also aim to gain a deeper understanding of the biological mechanisms involved in the pathways we have identified, which could lead to the validation of therapeutic targets or more personalized prevention strategies.

In the longer term, the goal is to develop clinical tools, such as blood tests, to detect cerebral small vessel disease earlier and provide better care for patients.

Find out more:

EM

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