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Intracellular Lewy inclusions containing aggregated \u03b1\u2010synuclein (\u03b1\u2010syn) represent a pathological hallmark of Parkinson's disease (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>). In most \u2013 but not all \u2013 studies published to date total <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> \u03b1\u2010syn concentrations have been found to be decreased in disorders related to \u03b1\u2010syn pathology, that is, <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>, dementia with Lewy bodies and multiple system atrophy. However, these reports show extensive signal overlap among tested individuals, thereby diminishing its potential for routine use in clinical practice.<\/jats:p><jats:p>To investigate potential biological (i.e., non\u2010technical) confounders of reported <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> levels for \u03b1\u2010syn, A\u03b242, and tau in <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> and related disorders, we carried out a methodical review of known factors that underlie signal variability and speculate on those that have not yet been tested. We discuss several biological factors, such as neuropathology, demographics, clinical phenotype, progression and duration of disease, concomitant illnesses and, last but not least, pharmacotherapy, which in isolation or combination can substantially alter values for <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> proteins of interest. Enhanced implementation of standardized clinical protocols, streamlined operating procedures, and further progress in the development of validated assays for <jats:styled-content style=\"fixed-case\">CSF<\/jats:styled-content> proteins have the potential to (i) inform us as to the pathogenesis of disease, (ii) support the laboratory\u2010based diagnosis for symptomatic subjects in the future, and (iii) facilitate breakthrough therapies to alter the course of neurodegenerative disorders, such as <jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content> and Alzheimer's disease.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p><jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc13390-fig-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\nCerebrospinal fluid (CSF) has been extensively studied to explore biochemical alterations in subjects with neurodegenerative disorders. To investigate potential biological confounders of reported CSF levels for \u03b1\u2010synuclein (\u03b1\u2010Syn), amyloid\u2010\u03b2 1\u201042(A\u03b242) and tau protein in Parkinson's disease and related disorders, we reviewed the current literature for known factors that underlie signal variability and speculate on those that have not yet been tested.<\/jats:p><jats:p><jats:bold>This article is part of a <\/jats:bold><jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/onlinelibrary.wiley.com\/journal\/10.1111\/(ISSN)1471-4159\/homepage\/special_issues.htm\">special issue on Parkinson disease<\/jats:ext-link><jats:bold>.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13390","type":"journal-article","created":{"date-parts":[[2015,10,10]],"date-time":"2015-10-10T11:25:41Z","timestamp":1444476341000},"page":"290-317","source":"Crossref","is-referenced-by-count":58,"title":["Biological confounders for the values of cerebrospinal fluid proteins in Parkinson's disease and related disorders"],"prefix":"10.1111","volume":"139","author":[{"given":"Brit","family":"Mollenhauer","sequence":"first","affiliation":[{"name":"Paracelsus\u2010Elena\u2010Klinik Kassel Germany"},{"name":"University Medical Center (Department of Neuropathology) Georg\u2010August University Goettingen Goettingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[{"name":"Centro Disturbi della Memoria\u2010 Unit\u00e0 Valutativa Alzheimer Clinica Neurologica Universit\u00e0 di Perugia Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Irena","family":"Rektorova","sequence":"additional","affiliation":[{"name":"Applied Neuroscience Group CEITEC MU Masaryk University Brno Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milica G.","family":"Kramberger","sequence":"additional","affiliation":[{"name":"Department of Neurology University Medical Center Ljubljana Ljubljana Slovenia"},{"name":"Division for Neurogeriatrics Department of NVS Karolinska Institutet Center for Alzheimer Research Stockholm Sweden"},{"name":"Centre for Age\u2010Related Medicine Stavanger University Hospital Stavanger Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Pikkarainen","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine \/ Neurology University of Eastern Finland Kuopio Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Walter J.","family":"Schulz\u2010Schaeffer","sequence":"additional","affiliation":[{"name":"University Medical Center (Department of Neuropathology) Georg\u2010August University Goettingen Goettingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dag","family":"Aarsland","sequence":"additional","affiliation":[{"name":"Division for Neurogeriatrics Department of NVS Karolinska Institutet Center for Alzheimer Research Stockholm Sweden"},{"name":"Centre for Age\u2010Related Medicine Stavanger University Hospital Stavanger Norway"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Per","family":"Svenningsson","sequence":"additional","affiliation":[{"name":"Department for Clinical Neuroscience Karolinska Institute Stockholm Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lucia","family":"Farotti","sequence":"additional","affiliation":[{"name":"Centro Disturbi della Memoria\u2010 Unit\u00e0 Valutativa Alzheimer Clinica Neurologica Universit\u00e0 di Perugia Perugia Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel M.","family":"Verbeek","sequence":"additional","affiliation":[{"name":"Department of Neurology Department of Laboratory Medicine Donders Institute for Brain, Cognition and Behaviour Radboud University Medical Centre Nijmegen The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael G.","family":"Schlossmacher","sequence":"additional","affiliation":[{"name":"Program in Neuroscience and Division of Neurology The Ottawa Hospital University of Ottawa Brain &amp; 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