{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T07:19:24Z","timestamp":1787555964217,"version":"build-2736575974"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T00:00:00Z","timestamp":1787529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Idiopathic normal pressure hydrocephalus (iNPH) is a potentially reversible neurological disorder whose diagnosis is complicated by clinical overlap with neurodegenerative diseases. Fluid biomarkers may provide insight into disease mechanisms and support differential diagnosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed a small exploratory study at the Neurology and Neurosurgery Sections of the University Hospital of Perugia, between 2024 and 2025, comparing cerebrospinal fluid (CSF) and plasma biomarkers among patients with iNPH, Alzheimer's disease (AD), Parkinson's disease (PD), and non-neurodegenerative controls (CTRL). CSF concentrations of amyloid-\u03b2 peptides (A\u03b242, A\u03b240, A\u03b242\/A\u03b240 ratio), tau proteins (p-tau 181 and t-tau) and neurofilament light chain (NfL) were measured. In plasma, amyloid-\u03b2 peptides (A\u03b242, A\u03b240, A\u03b242\/A\u03b240 ratio), tau proteins (p-tau 217), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed. Both CSF and plasma biomarkers were measured using standardized immunoassays. Group differences and correlations between CSF and plasma biomarkers were analyzed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CSF A\u03b240 levels were significantly lower in iNPH compared with all other groups (all p &amp;lt; 0.005), and showed preliminary apparent discrimination for iNPH, requiring external validation, with an AUC of 0.95, sensitivity of 95%, and specificity of 86% at a cut-off of 9,327.5 pg\/mL. AD patients were clearly distinguished from iNPH and the other groups by AD-specific changes in fluid biomarkers. CSF A\u03b242 levels were lower in iNPH than in CTRL (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.001) and PD (\n                      <jats:italic>p<\/jats:italic>\n                      = 0.009), while CSF p-tau181 and t-tau were decreased compared with AD (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001) and CTRL (\n                      <jats:italic>p<\/jats:italic>\n                      \u2264 0.024). The CSF A\u03b242\/A\u03b240 ratio remained preserved in iNPH, distinguishing it from AD (\n                      <jats:italic>p<\/jats:italic>\n                      &amp;lt; 0.001).\n                    <\/jats:p>\n                    <jats:p>\n                      Plasma NfL correlated strongly with CSF levels in each diagnostic group, including iNPH (\n                      <jats:italic>r<\/jats:italic>\n                      = 0.77,\n                      <jats:italic>p<\/jats:italic>\n                      = 0.0012), whereas plasma amyloid biomarkers poorly reflected CSF concentrations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>iNPH is associated with low CSF A\u03b240 levels, possibly reflecting altered CSF dynamics rather than a primary pathophysiological mechanism. In iNPH, plasma NfL showed a preliminary correlation with CSF NfL; however, larger age-adjusted studies are required before peripheral markers can be considered clinically informative in this setting.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnagi.2026.1866009","type":"journal-article","created":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T06:21:56Z","timestamp":1787552516000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Cerebrospinal fluid and plasma biomarkers in idiopathic normal pressure hydrocephalus: comparison with Alzheimer's and Parkinson's diseases"],"prefix":"10.3389","volume":"18","author":[{"given":"Francesca","family":"Pappafava","sequence":"first","affiliation":[{"name":"University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Gaetani","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo Maria","family":"Ottaviani","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Struttura Complessa Interaziendale di Neurochirurgia Perugia-Terni, Azienda Ospedaliera di Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Fiorucci","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Struttura Complessa Interaziendale di Neurochirurgia Perugia-Terni, Azienda Ospedaliera di Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanna","family":"Nardi","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola","family":"Salvadori","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alfredo","family":"Megaro","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federico","family":"Paolini Paoletti","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucilla","family":"Parnetti","sequence":"additional","affiliation":[{"name":"Section of Neurology, Department of Medicine and Surgery, University of Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlo","family":"Conti","sequence":"additional","affiliation":[{"name":"Neurosurgery Unit, Struttura Complessa Interaziendale di Neurochirurgia Perugia-Terni, Azienda Ospedaliera di Perugia","place":["Perugia, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,24]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.parkreldis.2020.11.009","article-title":"Altered glymphatic system in idiopathic normal pressure hydrocephalus","volume":"82","author":"Bae","year":"2021","journal-title":"Parkinsonism Relat. 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