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However, the relationship between CSF volume and protein levels remains largely unexplored. Moreover, the few existing studies provide conflicting findings, indicating the need for further research.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>Here, we explored the association between levels of 88 pre-selected CSF proteins and ventricular volume derived from magnetic resonance imaging (MRI) measurements in 157 cognitively healthy 70-year-olds from the H70 Gothenburg Birth Cohort Studies, including individuals with and without pathological levels of Alzheimer\u2019s disease (AD) CSF markers (<jats:italic>n<\/jats:italic>\u2009=\u2009123 and 34, respectively). Both left and right lateral, the inferior horn as well as the third and the fourth ventricular volumes were measured. Different antibody-based methods were employed for the protein measurements, with most being analyzed using a multiplex bead-based microarray technology. Furthermore, the associations between the protein levels and cortical thickness, fractional anisotropy, and mean diffusivity were assessed.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>CSF levels of many brain-derived proteins correlated with ventricular volumes in A-T- individuals, with lower levels in individuals with larger ventricles. The strongest negative correlations with total ventricular volume were observed for neurocan (NCAN) and neurosecretory protein VGF (rho = -0.34 for both). Significant negative correlations were observed also for amyloid beta (Ab) 38, Ab40, total tau (t-tau), and phosphorylated tau (p-tau), with correlation ranging between \u2212\u20090.34 and \u2212\u20090.28, while no association was observed between ventricular volumes and Ab42 or neurofilament light chain (NfL). Proteins with negative correlations to ventricular volumes further demonstrated negative correlations to mean diffusivity and positive correlation to fractional anisotropy. However, only weak or no correlations were observed between the CSF protein levels and cortical thickness. A\u2009+\u2009T\u2009+\u2009individuals demonstrated higher CSF protein levels compared to A-T- individuals with the most significant differences observed for neurogranin (NRGN) and synuclein beta (SNCB).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Our findings suggest that the levels of many brain-derived proteins in CSF may be subjected to dilution effects depending on the size of the brain ventricles in healthy individuals without AD pathology. This phenomenon could potentially contribute to the inter-individual variations observed in CSF proteomic studies.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12014-024-09517-1","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T07:40:57Z","timestamp":1733989257000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["CSF levels of brain-derived proteins correlate with brain ventricular volume in cognitively healthy 70-year-olds"],"prefix":"10.1186","volume":"21","author":[{"given":"Sofia","family":"Bergstr\u00f6m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ra","family":"Mravinacov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olof","family":"Lindberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Zettergren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Westman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars-Olof","family":"Wahlund","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Kern","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingmar","family":"Skoog","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"M\u00e5nberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,12,12]]},"reference":[{"issue":"6","key":"9517_CR1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1016\/j.anorl.2011.03.002","volume":"128","author":"L Sakka","year":"2011","unstructured":"Sakka L, Coll G, Chazal J. 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All participant and\/or their close relatives gave written informed consent to participate in the study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"HZ has served at scientific advisory boards and\/or as a consultant for Abbvie, Acumen, Alector, Alzinova, ALZPath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave, has given lectures in symposia sponsored by Alzecure, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, and Roche, and is a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program (outside submitted work). SK has served at scientific advisory boards, speaker and \/ or as consultant for Roche, Geras Solutions, Optoceutics, Biogen and Bioarctic.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"65"}}