# Unveiling the Proteomic Landscape of Extracellular Vesicles: Implications for Neurodegeneration and Neuroprotection

## TL;DR

This paper reviews how proteins in extracellular vesicles can help understand and treat brain diseases like Alzheimer's and Parkinson's.

## Contribution

The paper integrates recent EV proteomics advances to highlight their roles in neurodegeneration and potential as biomarkers and therapies.

## Key findings

- EVs carry disease-specific proteins like tau and alpha-synuclein in Alzheimer's and Parkinson's.
- EVs from different cell types can have protective or harmful effects in brain diseases.
- EV proteomics reveals biomarkers and pathways relevant to neurodegeneration and injury.

## Abstract

Extracellular vesicles (EVs) are instrumental mediators of intercellular communication and molecular exchange in neurodegenerative and neurovascular diseases. This review integrates recent advances in EV proteomics to elucidate their roles in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), traumatic brain injury (TBI), and ischemic stroke. Across these conditions, EVs carry disease‐relevant proteins that reflect and influence key pathological processes such as synaptic dysfunction, neuroinflammation, blood–brain barrier (BBB) disruption, and cell death. Proteomic profiling of brain‐ and biofluid‐derived EVs has uncovered specific biomarkers and signaling pathways, ranging from tau and α‐synuclein in AD and PD to mutant SOD1 in ALS and complement activation in stroke and TBI. Moreover, cell‐type‐specific EVs (e.g., from neurons, astrocytes, microglia, and stem cells) have been shown to exert either protective or deleterious effects, modulating apoptosis, axonal regeneration, and immune responses. Recent evidence highlights the translational potential of EVs as non‐invasive biomarkers and therapeutic vectors across multiple disorders. By mapping shared and divergent proteomic signatures in EVs, we review the mechanistic relevance and clinical utility of EVs in neurodegeneration and CNS injury.

Extracellular vesicles (EVs) are tiny, membrane‐covered packets that cells naturally release to send molecular information to one another. In the brain, they function as couriers that move proteins, lipids, and other signals between neurons, glial cells, and the blood–brain barrier. This review explains how studying the protein content of EVs helps scientists understand what is happening inside the brain during conditions such as Alzheimer's Parkinson's, amyotrophic lateral sclerosis (ALS), traumatic brain injury, and stroke. By analyzing EVs from blood, cerebrospinal fluid, or brain tissue, researchers can potentially detect early disease‐related changes, follow inflammatory processes, monitor the spread of harmful proteins, and identify molecules involved in either injury or repair. Because EVs travel through the bloodstream and can reach the brain, they are becoming valuable tools for earlier and more accurate diagnosis, and they are being considered as natural carriers for therapies that need to reach specific brain cells. EV proteomics is rapidly becoming a central strategy for both understanding and treating neurological disease.