Cerebrospinal Fluid: Novel Developed Biomarkers in Neurological Disease

M. Dessi, F. Duranti, M. Pieri, G. Sancesario, R. Zenobi, S. Bernardini

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

The cerebrospinal fluid (CSF) is a dynamic, metabolically active fluid that occupies the subarachnoid space and the ventricular system around the brain, and has many important functions. CSF is a promising body fluid for the search of biomarkers associated with neurological disease, because CSF has more physical contact with brain than any other fluid, and biochemical changes related to many pathologies may be reflected in the CSF. Although CSF is obtained by lumbar puncture, invasive and potentially painful for the patient, it is probably the most informative fluid in biomarkers discovery for neurological disease prognosis. Basic CSF diagnostics tests, such as the CSF/serum albumin ratio and CSF cell counts, have been used to diagnose inflammatory and infectious CNS disorders in adults and children for decades. The use of biomarkers is increasingly proposed as a method to refine the diagnosis and guide the treatment of numerous diseases. In this chapter, we review the development of candidate biomarkers in CSF and serum for different pathologies. We focus on established biomarkers, those that have been evaluated in several studies by different research groups, and we discuss their implementation in clinical routines and their potential role in clinical trials. Besides the state of art about what is known on classical CSF biomarkers for early diagnosis in routine clinical practice, there also are international research initiatives aimed at identifying new biomarkers for detection, and monitoring of pathological processes in the brain. Recently biomarkers are useful in detecting the preclinical as well as the symptomatic stages of Alzheimer Disease (AD). The core CSF biomarkers total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of b-amyloid (Ab42) reflect AD pathology, and are highly accurate in diagnosing AD with dementia and prodromal AD in mild cognitive impairment cases. Among recognized mediators, other new methods and tests can help highlight inflammatory or neurodegenerative processes in the CNS, accumulating evidence indicates that interleukin-6 (IL-6) is a new potential marker of CNS diseases. Another new test specific to diagnosing multiple sclerosis (MS) is the nephelometric assay for k free light chain determination and kFLC Index calculation in cerebrospinal fluid and serum. Only the CSF oliglonal band and IgG index are currently used to assist with MS diagnosis. The new nephelometric test may be a useful procedure for detection, potentially for monitoring intrathecal immunoglobulin synthesis, and to permit a rapid discriminatory diagnosis of MS. In this chapter, we discuss the recent advancements of clinical diagnostic CSF tests with particular emphasis on possible new biomarkers for monitoring the early development of CNS disease before significant cognitive dysfunction and also to stratify clinical prognosis. Finally the rationale for the use of CSF biomarkers to identify and monitor the mechanism of action of new drug candidates is also outlined in this chapter.

Original languageEnglish
Title of host publicationCerebrospinal Fluid: Clinical Biochemistry, Physiology and Diagnostic Characteristics
PublisherNova Science Publishers, Inc.
Pages15-60
Number of pages46
ISBN (Print)9781631179099, 9781631179082
Publication statusPublished - Apr 1 2014

ASJC Scopus subject areas

  • Neuroscience(all)

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