Liquid Biopsy in Neurological Diseases

Abstract

The most recent and non-invasive approach for studying early-stage biomarkers is liquid biopsy. This implies the extraction and analysis of non-solid biological tissues (serum, plasma, saliva, urine, and cerebrospinal fluid) without undergoing invasive procedures to determine disease prognosis. Liquid biopsy can be used for the screening of several components, such as extracellular vesicles, microRNAs, cell-free DNA, cell-free mitochondrial and nuclear DNA, circulating tumour cells, circulating tumour DNA, transfer RNA, and circular DNA or RNA derived from body fluids. Its application includes early disease diagnosis, the surveillance of disease activity, and treatment response monitoring, with growing evidence for validating this methodology in cancer, liver disease, and central nervous system (CNS) disorders. This review will provide an overview of mentioned liquid biopsy components, which could serve as valuable biomarkers for the evaluation of complex neurological conditions, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, epilepsy, stroke, traumatic brain injury, CNS tumours, and neuroinfectious diseases. Furthermore, this review highlights the future directions and potential limitations associated with liquid biopsy.

Keywords: cfDNA; liquid biopsy; microRNA; neurological diseases.

Figure 1

Overview of liquid biopsy. Figure showing brain–periphery communication. Central nervous system (CNS) cell populations, including neurons, astrocytes, and glial cells, release the principal elements of liquid biopsy components, including extracellular vesicles (micro-vesicles, exosomes, and apoptotic bodies), transfer-RNA (tRNA), circular RNA (circRNA), and cell-free (cfDNA) within the CNS. The most studied component of liquid biopsy constitutes exosomes. It contains functional microRNA (miRNA) and small RNA. A process of membrane vesicle trafficking performs the transfer of exosomes from the donor cell to the recipient cells. tRNA mainly comprises fewer than 90 nucleotides. tRNA-derived RNA fragments (t-RFs) act as essential mediators of CNS and immune communications via t-RFs. CircRNA is a single-stranded RNA, primarily present in circular form. Another component of liquid biopsy includes cell-free DNA (cfDNA), composed of double-helix DNA fragments released from CNS cells/nucleated cells and circulating freely in the bloodstream. Cell-free mitochondrial (cf-mtDNA) is a double-stranded fragment produced by dysfunctional mitochondria. Circulating tumour DNA (ctDNA) is produced by tumour cells; because of their half-life, these are real-time indicators of disease status in the body.