2025/02/26

A study reveals that exosomes are surrogate markers of metabolic alterations of the brain in Alzheimer’s disease

Alzheimer’s disease, the most common neurodegenerative disorder, is deeply linked to metabolic changes that are key to its development and progression.

The study, published in the Journal of Extracellular Vesicles, analyzes the metabolic profiles of brain tissue and extracellular vesicles obtained from those tissues in Alzheimer’s patients, uncovering novel methods to study metabolic mechanisms involved in the disease. 

This research provides new insights into the metabolic processes underlying Alzheimer’s, identifying potential biomarkers and paving the way for the development of more effective diagnostic and therapeutic tools.

A team of researchers from CIC bioGUNE, member of BRTA, led by Ikerbasque Research Professor Juan Manuel Falcón, in collaboration with CIBERehd, BIOEF and the Hospitals of Cruces and Txagorritxu has published groundbreaking findings in Journal of Extracellular Vesicles. The study investigates the metabolic profiles of brain tissue and brain-derived extracellular vesicles from Alzheimer’s patients, offering fresh perspectives on the metabolic alterations involved in this pathology.

The research reveals significant disruptions in key metabolic pathways, such as the biosynthesis of phenylalanine, tyrosine, and tryptophan, which may be affected in Alzheimer’s disease. Furthermore, researchers identified differences in the levels of certain metabolites between Alzheimer’s patients and healthy individuals, suggesting their potential diagnostic and therapeutic value.

To conduct the study, scientists optimize the isolation of exosomes from human brain tissue and utilized an untargeted metabolomics approach, which allows for the comprehensive analysis of metabolites in a biological sample without specific targets. This method was applied to both the brain tissue and the exosomes derived from the brain tissues, enabling the detection of significant differences between the groups studied. Advanced statistical analyses identified the most relevant metabolites for distinguishing between patients and controls, reinforcing their role as potential biomarkers.

Extracellular vesicles play a crucial role in regulating pathophysiological processes and provide information about their originating cells in a non-invasive manner. In this context, the metabolomic analysis of these vesicles offers an innovative approach to understanding the metabolic processes involved in Alzheimer’s disease while highlighting their potential as a tool for detecting and studying the condition.

This study is the first to apply untargeted metabolomics to analyze the polar metabolome in both brain tissue and brain-derived extracellular vesicles from Alzheimer’s patients. The findings underscore the importance of studying extracellular vesicles to better understand the metabolic alterations associated with the disease and their correlation with brain tissue.

"This collaborative work establish a method to obtain exosomes from human brain tissue and highlight that extracellular vesicles in the central nervous system can be an important resource to understand metabolism of neurodegenerative diseases," stated Prof. Juan Manuel Falcón.

The research was conducted in collaboration with several institutions, including the CITA-Alzheimer Foundation, the Institute of Biomedicine, Bioaraba, and various hospitals and universities in the Basque Country, as well as CIBERehd and the Basque Foundation for Science Ikerbasque. The project received financial support from the Alzheimer’s Association through grant AARG-NTF-22-968911 and the Deutsche Forschungsgemeinschaft (DFG) via grant 471840646.

This significant advancement highlights CIC bioGUNE’s commitment to Alzheimer’s research, providing new tools and knowledge that could contribute to the development of more effective diagnostic and therapeutic strategies.

Reference: Patricia Hernandez, Elisabeth Rackles, Oihane E. Alboniga, Pablo Martínez-Lage, Emma N. Camacho, Arantza Onaindia, Manuel Fernandez, Ana Talamillo, Juan M. Falcon-Perez. Metabolic Profiling of Brain Tissue and Brain-Derived Extracellular Vesicles in Alzheimer’s Disease. Journal of Extracellular Vesicles. DOI: 10.1002/jev2.70043.

Image generated by AI, using DALLE. Desciphering the role of the exosomes in the metabolic alterations happening in Alzheimer"s disease will offer novel diagnostics tools and therapies.

About CIC bioGUNE

The Centre for Cooperative Research in Biosciences (CIC bioGUNE), member of the Basque Research & Technology Alliance (BRTA), located in the Bizkaia Technology Park, is a biomedical research organisation conducting cutting-edge research at the interface between structural, molecular and cell biology, with a particular focus on generating knowledge on the molecular bases of disease, for use in the development of new diagnostic methods and advanced therapies.

About Ikerbasque

Ikerbasque - Basque Foundation for Science - is the result of an initiative of the Department of Education of the Basque Government that aims to reinforce the commitment to scientific research by attracting, recovering and consolidating excellent researchers from all over the world. Currently, it is a consolidated organization that has 290 researchers/s, who develop their work in all fields of knowledge.

About BRTA

BRTA is an alliance of 4 collaborative research centres (CIC bioGUNE, CIC nanoGUNE, CIC biomaGUNE y CIC energiGUNE) and 13 technology centres (Azterlan, Azti, Ceit, Cidetec, Gaiker, Ideko, Ikerlan, Leartiker, Lortek, Neiker, Tecnalia, Tekniker y Vicomtech) with the main objective of developing advanced technological solutions for the Basque corporate fabric.

With the support of the Basque Government, the SPRI Group and the Provincial Councils of the three territories, the alliance seeks to promote collaboration between the research centres, strengthen the conditions to generate and transfer knowledge to companies, contributing to their competitiveness and outspreading the Basque scientific-technological capacity abroad.

BRTA has a workforce of 3,500 professionals, executes 22% of the Basque Country's R&D investment, registers an annual turnover of more than 300 million euros and generates 100 European and international patents per year.

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