{"entity": "publication", "iuid": "934abbdaa93042c99b863e927fd9b3eb", "timestamp": "2026-04-10T13:45:10.491Z", "links": {"self": {"href": "https://publications.scilifelab.se/publication/934abbdaa93042c99b863e927fd9b3eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/934abbdaa93042c99b863e927fd9b3eb"}}, "title": "Targeted CSF metabolomics and conformal prediction improve diagnostic accuracy of normal pressure hydrocephalus.", "authors": [{"family": "Hofling", "given": "Ulrika", "initials": "U"}, {"family": "Jakobsson", "given": "Jenny", "initials": "J"}, {"family": "Erngren", "given": "Ida", "initials": "I"}, {"family": "Ekman", "given": "Oskar", "initials": "O"}, {"family": "Freyhult", "given": "Eva", "initials": "E"}, {"family": "Sreenivasan", "given": "Akshai Parakkal", "initials": "AP"}, {"family": "Siljebo", "given": "Jakob", "initials": "J"}, {"family": "Libard", "given": "Sylwia", "initials": "S"}, {"family": "Kilander", "given": "Lena", "initials": "L"}, {"family": "L\u00f6wenmark", "given": "Malin", "initials": "M"}, {"family": "Ingelsson", "given": "Martin", "initials": "M"}, {"family": "Kultima", "given": "Kim", "initials": "K"}, {"family": "Virhammar", "given": "Johan", "initials": "J"}], "type": "journal article", "published": "2026-02-07", "journal": {"title": "Fluids Barriers CNS", "issn": "2045-8118", "volume": "23", "issue": "1", "issn-l": null}, "abstract": "Idiopathic normal pressure hydrocephalus (iNPH) is a progressive but treatable neurological disorder. Yet, diagnosis is often confounded by overlapping symptoms and biomarker profiles with Alzheimer\u2019s disease (AD), mild cognitive impairment (MCI), and frontotemporal dementia (FTD). We aimed to determine whether cerebrospinal fluid (CSF) metabolomic profiling, combined with uncertainty-aware machine learning using conformal prediction (CP), could improve diagnostic differentiation of iNPH.\n\nCSF samples were collected from 120 patients with iNPH, 44 healthy controls, and 152 individuals with AD, MCI, or FTD. Targeted metabolomics of 59 metabolites was performed using liquid chromatography\u2013high-resolution mass spectrometry. Group differences were assessed using age- and sex-adjusted regression models. Multivariate classification with partial least squares discriminant analysis (PLS-DA) incorporated metabolites, demographics, and conventional biomarkers (amyloid-\u03b242, tau, phosphorylated tau). CP was applied to address individual-level diagnostic uncertainty.\n\nEight metabolites (proline, threonine, histidine, tyrosine, tryptophan, isobutyrylcarnitine, citric acid, and dehydroascorbic acid) were consistently reduced in iNPH (q < 0.05), independent of ventricular volume and cortical tau or amyloid-\u03b2 pathology. An integrated PLS-DA model combining metabolomic, demographic, and AD-biomarker data achieved excellent discrimination (AUC = 0.97). CP provided calibrated case-level confidence, identifying clear-cut and uncertain cases while maintaining high accuracy (94% for iNPH, 97% for not-iNPH).\n\niNPH exhibits a distinct CSF metabolomic signature reflecting altered amino acid metabolism, mitochondrial function, and oxidative stress. Integrating metabolomic data with established biomarkers enhances diagnostic accuracy, while CP adds individualized uncertainty estimates to improve diagnostic confidence and guide treatment decisions.\n\nThe online version contains supplementary material available at 10.1186/s12987-026-00771-z.", "doi": "10.1186/s12987-026-00771-z", "pmid": "41654915", "labels": {"Bioinformatics (NBIS)": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12930833"}, {"db": "pii", "key": "10.1186/s12987-026-00771-z"}], "notes": [], "created": "2026-04-10T07:10:24.128Z", "modified": "2026-04-10T07:10:24.131Z"}