Metabolites and Biomarker Compounds of Neurodegenerative Diseases in Cerebrospinal Fluid

Abstract

Despite recent advances in diagnostic procedures for neurological disorders, it is still difficult to definitively diagnose some neurodegenerative diseases without neuropathological examination of autopsied brain tissue. As pathological processes in the brain are frequently reflected in the components of cerebrospinal fluid (CSF), CSF samples are sometimes useful for diagnosis. After CSF is secreted from the choroid plexus epithelial cells in the ventricles, some flows in the brain, some is mixed with intracerebral interstitial fluid, and some is excreted through two major drainage pathways, i.e., the intravascular periarterial drainage pathway and the glymphatic system. Accordingly, substances produced by metabolic and pathological processes in the brain may be detectable in CSF. Many papers have reported changes in the concentration of substances in the CSF of patients with metabolic and neurological disorders, some of which can be useful biomarkers of the disorders. In this paper, we show the significance of glucose- and neurotransmitter-related CSF metabolites, considering their transporters in the choroid plexus; summarize the reported candidates of CSF biomarkers for neurodegenerative diseases, including amyloid-β, tau, α-synuclein, microRNAs, and mitochondrial DNA; and evaluate their potential as efficient diagnostic tools.

The role of ncRNAs in depression

“…CSF fills the ventricles, subarachnoid space and central canal of the spinal cord [ 61 ]. The choroid plexus located in the ventricle produces CSF, which is extracellular fluid, much like lymph and plasma [ [62] , [63] , [64] ]. According to a meta-regression analysis, the identification of miRNA expression in CSF significantly increases diagnostic accuracy [ 65 ].…”

Epidural and Intrathecal Drug Delivery in Rats and Mice for Experimental Research: Fundamental Concepts, Techniques, Precaution, and Application

“…CSF is a colorless fluid that is secreted by the choroid plexus into the ventricular cavities (80%) and by other structures, such as the brain parenchyma (20%) [31]. Compared to blood plasma, CSF contains a higher concentration of sodium, chloride, and magnesium ions and a lower concentration of glucose; proteins; amino acids; uric acid; and calcium, phosphate, and potassium ions [32]. The rate of CSF production and the total CSF volume vary across species (Table 2), but CSF circulates similarly inside the ventricular system and the cranial and spinal subarachnoid spaces.…”

Common immunopathogenesis of central nervous system diseases: the protein-homeostasis-system hypothesis

“…CSF profiles, such as cell counts, protein and lactate levels, the CSF/plasma albumin ratio, and culture and polymerase chain reaction assays are used to diagnose CNS infections and inflammatory conditions. The components of CSF have been extensively evaluated as biomarkers for various neurological disorders, including infections, inflammatory or neurodegenerative disorders, seizure disorders, tumors, traumatic brain injury, and hydrocephalus [16][17][18]. The biomarkers of each neurologic disease are helpful for diagnosing and evaluating disease processes and include proteins (such as immunoglobulins or the oligoclonal band, tau protein, glial fibrillary acidic protein, neuronspecific enolase, neopterin, S100β, and interleukins) and other small components such as micro RNAs, mitochondrial DNA, reactive oxygen species, and changed level of monoamine metabolites in children and adults [16][17][18].…”

“…The components of CSF have been extensively evaluated as biomarkers for various neurological disorders, including infections, inflammatory or neurodegenerative disorders, seizure disorders, tumors, traumatic brain injury, and hydrocephalus [16][17][18]. The biomarkers of each neurologic disease are helpful for diagnosing and evaluating disease processes and include proteins (such as immunoglobulins or the oligoclonal band, tau protein, glial fibrillary acidic protein, neuronspecific enolase, neopterin, S100β, and interleukins) and other small components such as micro RNAs, mitochondrial DNA, reactive oxygen species, and changed level of monoamine metabolites in children and adults [16][17][18]. Because cells in the CNS communicate through the CSF, most biomarkers, including immune-associated proteins and DAMPs, are associated with activated neuroimmune cells, such as microglia and astrocytes, and injured target CNS cells.…”