Analysis of Synaptic Plasticity Biomarkers in Neuron-Derived Extracellular Vesicles Isolated from Human Plasma.

• Grant number: 24/23291-5
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: June 24, 2025
• End date: August 02, 2025
• Field of knowledge: Health Sciences - Medicine - Pathological Anatomy and Clinical Pathology
• Principal Investigator: Fernando Cendes
• Grantee: Isadora Cristina Ribeiro
• Supervisor: Fernanda Guarino de Felice
• Host Institution: Faculdade de Ciências Médicas (FCM). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
• Institution abroad: Queen's University, Canada
• Associated to the scholarship: 24/19135-8 - Plasma biomarkers and neuroimaging in the Alzheimer's disease continuum., BP.PD

Abstract

Introduction: Irisin is a myokine induced by muscle contraction that has recently been proposed as a potential biomarker of synaptic plasticity. It promotes the expression of brain-derived neurotrophic factor (BDNF), a protein critical for synaptic plasticity. Individuals with Alzheimer's disease (AD) not only exhibit alterations in disease-specific biomarkers, such as tau protein and amyloid-beta, but also present reduced levels of irisin and BDNF. Biomarkers such as irisin and BDNF, which can be stimulated by physical exercise, have garnered increasing attention in recent research due to their beneficial effects on cognition and their association with the limitation of amyloid-beta accumulation in the hippocampus. The analysis of AD biomarkers in cerebrospinal fluid (CSF) is an effective method for monitoring brain alterations, but it is both invasive and not easily accessible. Blood sampling offers a more accessible and minimally invasive alternative. However, traditional blood biomarker analyses may reflect concentrations in peripheral tissues, limiting their specificity for brain-related changes. Recent advances in biomarker research have emphasized the use of extracellular vesicles (EVs) isolated from plasma. Evidence indicates that neuron-derived EVs (NDEVs) can cross the blood-brain barrier (BBB), making them a promising in vivo tool for investigating brain-related biomarkers. Our hypothesis is that physical exercise modulates irisin and BDNF levels in the brain, thereby altering their concentrations in NDEVs. Objective: The aim of this study is to determine whether chronic physical training affects irisin and BDNF concentrations in NDEVs from healthy young adults. Methods: To address this, 24 participants will be divided into two groups: a physical training group (n = 12) and a sedentary control group (n = 12). The intervention group will undergo a high-intensity interval training (HIIT) protocol, with blood samples collected one day before and one day after the intervention. Plasma will be isolated, and NDEVs will be selected through immunoprecipitation using antibodies specific for synaptosome-associated protein 25 (SNAP-25), which is highly expressed in the brain. Irisin and BDNF concentrations will be quantified using ELISA immunoassays, following the manufacturer's protocols. Results will be compared both pre- and post-intervention and between the training and control groups.