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The present work presents the development and validation of an inductively coupled plasma tandem mass spectrometry (ICP\u2010MS\/MS) based method for multielemental determination in CSF, including metals and metalloids as analytes. As a proof of concept, the importance of the CSF element determination was evaluated in a cohort of patients with AD (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200920) and non\u2010AD controls (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200919) who displayed typical levels of core CSF biomarkers (A\u03b242, P\u2010tau, and total\u2010tau). Discrete sample introduction ICP\u2010MS\/MS procedure was effective for accurate and precise CSF analysis. The methodology provided better sensitivities and limits of detection than a conventional one based on sample dilution and analysis in continuous sample introduction mode, while only requiring a 20\u2009\u03bcL CSF sample volume. A total of 24 elements were encountered and quantified in CSF, with reduced levels of Mn, Cr, Se, Fe, and Zn in the CSF from AD patients and increased levels of Ag and Bi, compared with non\u2010AD patients. Particularly, Mn fully discriminated AD from non\u2010AD subjects, with binary regression analysis indicating that Mn was the most effective element to distinguish between AD and non\u2010AD groups. Furthermore, distinctive correlation profiles were found between AD and non\u2010AD controls for elements with AD core biomarkers and the alternative amyloidogenic sAPP\u03b2 fragment. Quantitative determination of metals, metalloids and non\u2010metals displays differences associated with pathological status, serving as additional biomarkers for neurological diseases.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc70307-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  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