Neuron-derived extracellular vesicle-based diagnostics for Tau and Alzheimer’s disease

Elsevier, Brain Network Disorders, Volume 1, Issue 3, September 2025, Pages 150-166
Authors: 
Subashchandrabose Chinnathambi, Murugappan Kumarappan, Sneha Malik, Gowshika Velmurugan, Madhura Chandrashekar

Extracellular vesicles (EVs) are defined as vesicles formed from lipid bilayers secreted by various cells. These EVs act as mediators between cells and transport proteinsgenetic material, and lipids. They display significant heterogeneous and contain cell-specific markers. In the central nervous system, particularly in the brain, EVs are secreted primarily by neurons, astrocytes, microglia, and oligodendrocytes. Their involvement in neurological diseases has been extensively investigated. Various aspects of EVs have been examined to understand disease progression and modulation, particularly in neurodegenerative neurological diseases. In neurodegenerative diseases, EVs carry pathological proteins, facilitating protein spreading and neuroinflammation. In Alzheimer’s disease (AD), these vesicles carry Tau and amyloid-β proteins, causing their deposition and increasing the inflammatory response. Neuron-derived extracellular vesicles (NDEVs) have diagnostic potential as they contain pathological proteins central to the disease. Their observation in bodily fluids such as plasma and serum adds an advantage to their use as minimally invasive biomarkers. The levels of NDEV proteins can be measured to distinguish patients with AD from healthy controls. In addition, they can be used to predict disease development 10 years prior to clinical onset. Comparative analyses of the micro ribonucleic acids (miRNAs) and lipids present in NDEVs between patients with AD and controls have been performed. Many researchers have suggested that NDEVs could be utilized as AD diagnostic biomarkers because of their high potential for biomolecular differences.