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  • Orduña Dolado, AnnaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas (author)

Effects of time of the day at sampling on CSF and plasma levels of Alzheimer' disease biomarkers

  • Article/chapterEnglish2024

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  • 2024

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  • LIBRIS-ID:oai:gup.ub.gu.se/339681
  • https://gup.ub.gu.se/publication/339681URI
  • https://doi.org/10.1186/s13195-024-01503-xDOI
  • https://lup.lub.lu.se/record/41b55426-ccb6-4afb-b1d5-cf789325ba76URI

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  • Language:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

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  • Background Studies suggest that cerebrospinal fluid (CSF) levels of amyloid-beta (A beta)42 and A beta 40 present a circadian rhythm. However sustained sampling of large volumes of CSF with indwelling intrathecal catheters used in most of these studies might have affected CSF dynamics and thereby confounded the observed fluctuations in the biomarker levels. Methods We included 38 individuals with either normal (N = 20) or abnormal (N = 18) CSF A beta 42/A beta 40 levels at baseline. CSF and plasma were collected at two visits separated by an average of 53 days with lumbar punctures and venipunctures performed either in the morning or evening. At the first visit, sample collection was performed in the morning for 17 participants and the order was reversed for the remaining 21 participants. CSF and plasma samples were analyzed for Alzheimer' disease (AD) biomarkers, including A beta 42, A beta 40, GFAP, NfL p-tau181, p-tau217, p-tau231 and t-tau. CSF samples were also tested using mass spectrometry for 22 synaptic and endo-lysosomal proteins. Results CSF A beta 42 (mean difference [MD], 0.21 ng/mL; p = 0.038), CSF A beta 40 (MD, 1.85 ng/mL; p < 0.001), plasma A beta 42 (MD, 1.65 pg/mL; p = 0.002) and plasma A beta 40 (MD, 0.01 ng/mL, p = 0.002) were increased by 4.2-17.0% in evening compared with morning samples. Further, CSF levels of 14 synaptic and endo-lysosomal proteins, including neurogranin and neuronal pentraxin-1, were increased by 4.5-13.3% in the evening samples (MDrange, 0.02-0.56 fmol/l; p < 0.042). However, no significant differences were found between morning and evening levels for the A beta 42/A beta 40 ratio, different p-tau variants, GFAP and NfL. There were no significant interaction between sampling time and A beta status for any of the biomarkers, except that CSF t-tau was increased (by 5.74%) in the evening samples compared to the morning samples in A beta-positive (MD, 16.46 ng/ml; p = 0.009) but not A beta-negative participants (MD, 1.89 ng/ml; p = 0.47). There were no significant interactions between sampling time and order in which samples were obtained. Discussion Our findings provide evidence for diurnal fluctuations in A beta peptide levels, both in CSF and plasma, while CSF and plasma p-tau, GFAP and NfL were unaffected. Importantly, A beta 42/A beta 40 ratio remained unaltered, suggesting that it is more suitable for implementation in clinical workup than individual A beta peptides. Additionally, we show that CSF levels of many synaptic and endo-lysosomal proteins presented a diurnal rhythm, implying a build-up of neuronal activity markers during the day. These results will guide the development of unified sample collection procedures to avoid effects of diurnal variation for future implementation of AD biomarkers in clinical practice and drug trials.

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  • Stomrud, ErikLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital(Swepub:lu)med-esr (author)
  • Ashton, Nicholas J.Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,King's College London,Sahlgrenska Academy,Stavanger University Hospital(Swepub:gu)xashtn (author)
  • Nilsson, Johanna,1993Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Sahlgrenska University Hospital(Swepub:gu)xnijoy (author)
  • Quijano-Rubio, Clara (author)
  • Jethwa, AlexanderRoche Diagnostics, Germany (author)
  • Scheeren Brum, Wagner,1997Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Federal University of Rio Grande do Sul,Sahlgrenska Academy(Swepub:gu)xschew (author)
  • Brinkmalm-Westman, Ann,1966Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Sahlgrenska University Hospital(Swepub:gu)xbrian (author)
  • Zetterberg, Henrik,1973Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,University College London,Sahlgrenska University Hospital,University of Wisconsin-Madison(Swepub:lu)med-hiz (author)
  • Blennow, Kaj,1958Gothenburg University,Göteborgs universitet,Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi,Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry,Sahlgrenska Academy,Pitié-Salpêtrière University Hospital,Sahlgrenska University Hospital,University of Science and Technology of China(Swepub:lu)med-kbw (author)
  • Janelidze, ShorenaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas(Swepub:lu)nkir-sje (author)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,LU profilområde: Proaktivt åldrande,Lunds universitets profilområden,Clinical Memory Research,Lund University Research Groups,LU Profile Area: Proactive Ageing,Lund University Profile areas,Skåne University Hospital(Swepub:lu)mphy-ohn (author)
  • Klinisk minnesforskningForskargrupper vid Lunds universitet (creator_code:org_t)

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  • In:ALZHEIMERS RESEARCH & THERAPY16:11758-9193

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