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Cerebrospinal fluid biomarkers for neurodegenerative disorders

1 Abstract Neurodegenerative diseases are one of the major world causes of morbidity and mortality, and giving the dramatic raise in life expectancy, they are reaching epidemic proportions. These disorders form a heterogeneous group, ranging from multi-factorial dementias to rare monogenic inherited proteopathies, but they all are progressive and so far lethal, since there are no disease-modifying therapies presently available. Therefore, major research efforts are in progress for developing effective therapies, but in order to achieve this goal there is an imperative need of consistent tools for diagnosis, prognosis and monitoring drug effects and efficacy. Biomarkers have the potential to respond to all these requirements and its research is a rapidly advancing field, supported by some cases of success for other diseases, in different fields like oncology and cardiology. Pathological alterations in the brain or central nervous system could be monitored by analysis of cerebrospinal fluid and several biomarkers in this fluid have been proposed. However, almost none have reached validation and for that reason they are still not used in clinical routine. Several problems regarding lack of longitudinal studies or reproducibility between reports are still waiting to be solved. In a near future this could happen by more intensive collaboration between research centers, industry and government in different countries, in joint initiatives. This review summarizes the most relevant CSF biomarker candidates for Alzheimer's and Parkinson's disease, Amyotrophic lateral sclerosis, Huntington's and Machado Joseph disease. It also briefly passes through biomarker definitions and concepts, beyond the current limitations in this investigation area.