The Potential of Liquid Biopsy of the Brain Using Blood Extracellular Vesicles: The First Step Toward Effective Neuropro
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REVIEW ARTICLE
The Potential of Liquid Biopsy of the Brain Using Blood Extracellular Vesicles: The First Step Toward Effective Neuroprotection Against Neurodegenerative Diseases Hanin Abdel‑Haq1 Accepted: 2 September 2020 © Springer Nature Switzerland AG 2020
Abstract Early diagnosis and biomarker-based ante-mortem tests are essential in efforts against the development of neurodegenerative diseases and can be considered primary neuroprotective measures. Blood is the ideal biofluid for a routine ante-mortem screening test. However, biomarker discovery in the blood is particularly difficult because of interference from factors both intrinsic and extrinsic to blood with the detection of hallmark neurodegenerative biomarkers, such as the pathological prion protein, amyloid-β, and others. Blood extracellular vesicles (EVs), such as exosomes, are cell-derived vesicles released into the blood from all parts of the body (including the brain and spinal cord). They are an enriched source of neural-derived EVs containing neurodegenerative biomarkers that mirror (in the blood) the condition present in the brain. The feasibility of using, and the reliability of, neural-derived blood EVs (NDBEVs) as a method of diagnosing Alzheimer disease and other neurodegenerative diseases has been assessed in strong proof-of-concept studies. Results from these studies strongly suggest that NDBEVs might represent the right strategy for specific, reliable, and early diagnosis of neurodegenerative diseases. Based on these results, NDBEVs might enable the creation of an ante-mortem blood test (liquid biopsy of the brain) for neurodegenerative diseases. This would enormously accelerate the therapy of neurodegenerative diseases. This review highlights the powerful potential of liquid biopsy of the brain using NDBEVs for early diagnosis and treatment of neurodegenerative diseases, and the challenges and limitations related to the identification of clinically applicable EV (exosomal) biomarkers using blood are discussed.
1 Introduction Neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and prion disease are usually only diagnosed once the brain is markedly damaged [1, 2]. Additionally, the affected population continues to increase in number, with a consequent increased burden on families, society, the economy, and public health. For these reasons and because effective treatment is unlikely once cognitive impairment has begun, early diagnosis of neurodegenerative diseases is essential. Early diagnosis might offer the first opportunity for neuroprotection against the definitive development of * Hanin Abdel‑Haq [email protected] 1
National Center for Drug Research and Evaluation, Istituto Superiore di Sanità, Viale Regina Elena, 299, 00161 Rome, Italy
Key Points An ante-mortem biomarker-based blood test for neurodegenerative diseases is potentially feasible. Amyloid-β (Aβ)-42, T-tau, and P-T181-tau could be the most predictive biomarkers for brain cognitive performanc
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