BIOPEXAL - Biomarkers of plasma exosomes for the early diagnosis of prodromal Alzheimer's disease

Alzheimer's disease is the most common form of dementia worldwide and its prevalence is increasing exponentially. A differential diagnosis in the early stages of the disease is one of the major challenges in routine clinical practice.

The invasive nature and high cost of current Alzheimer's diagnostic techniques have sparked a growing scientific interest in plasma biomarkers and, in particular, plasma exosomes. The plasma nature of these biomarkers means that they are extracted from blood plasma through a simple routine analysis, being more affordable and non-invasive than neuroimaging studies, PET radiotracers and cerebrospinal fluid biomarkers.

Exosomes: extracellular snitches

Exosomes are extracellular vesicles synthesized by most cells that play an important role in cell communication. This means that they carry information from all the cells in the body and enable these cells to communicate with each other. Exosomes are secreted by cells and contain nucleic acids (RNA) and proteins specific to the cell of origin, reflecting not only the cell type from which they originate but also their current state.

Recent scientific evidence describes that exosomes in the blood (plasma exosomes) are capable of reflecting the molecular alterations that occur centrally at different stages of Alzheimer's disease development and, therefore, could serve as peripheral biomarkers of the disease.

Thus, by analyzing the content of exosomes, we want to find a protein pattern that is indicative of different stages of cognitive impairment and its completion or not in Alzheimer's disease. Differences in the biomarker profile of the exosomes of patients with mild cognitive impairment who progress to Alzheimer's disease and those who do not, could be key to an early differential diagnosis.

Why have we designed the BIOPEXAL project?

The BIOPEXAL project has two main objectives:

1. To evaluate the potential of plasma exosomes as a tool for early diagnosis and monitoring of Alzheimer's disease.
2. To evaluate the potential of plasma exosomes as a tool for the propagation of pathological hallmarks of Alzheimer's disease.

Biomarker profiling of plasma exosomes

The first phase of the project is carried out at Ace Alzheimer Center Barcelona and focuses on the study of the protein content of plasma exosomes of patients at different stages of the disease (patients with subjective memory complaints, with mild cognitive impairment and with dementia caused by Alzheimer's disease).

The procedure consists of extracting plasma exosomes from blood samples of these patients and measuring the concentrations of 184 proteins involved in Alzheimer's disease and related to inflammation and neurodegenerative processes. The aim is to evaluate whether there is a pattern of biomarkers in plasma exosomes that would allow earlier identification of those patients with mild cognitive impairment who progress to dementia and those who do not.

Potential for propagation of Alzheimer's pathological hallmarks

The second phase of the study is carried out in the UB laboratories and studies the role of plasma exosomes in the spread of altered molecules in Alzheimer's disease throughout the brain.

The procedure consists of isolating plasma exosomes from Alzheimer's patients and incubating them in in vitro and in vivo models. The aim is to determine the influence of exposure to exosomes of different phenotypes in the development of the disease on the molecular mechanisms of the cells and to evaluate the subsequent cognitive and memory alterations.

Relevance of the BIOPEXAL project

• Scientific and therapeutic research: BIOPEXAL will have a major impact on the search for new diagnostic strategies based on early identification of the development of dementia, as well as on the standardization of protocols for preventive interventions. This project has the potential to shed light in the field of Alzheimer's prognosis, early diagnosis and personalized treatment.
• Socioeconomic impact: new plasma biomarkers will enable more cost-effective diagnosis, better informed medical decisions, and improved therapeutic outcomes through early diagnosis and personalized treatment. Their interest lies in the fact that they are affordable, non-invasive for the patient, and easy to obtain in any primary care center. Therefore, they help reduce the burden on the healthcare system and increase economic productivity.