The potential dual role of tau phosphorylation: plasma phosphorylated-tau217 in newborns and Alzheimer's disease

Fernando Gonzalez-Ortiz^{1

2

3}, Jakub Vávra¹, Emma Payne⁴, Bjørn-Eivind Kirsebom^{5

6

7}, Ulrika Sjöbom^{8

9}, Cristiano Santos², Jordi Júlvez¹⁰, Kaitlin Kramer^{11

12}, David Zalcberg^{11

12}, Laia Montoliu-Gaya¹, Michael Turton¹³, Peter Harrison¹³, Ann Hellström⁹, Henrik Zetterberg^{1

2

14

15

16

17}, Tormod Fladby^{7

18}, Marc Suárez-Calvet^{19

20

21}, Robert D Sanders^{11

12

22

23}, Kaj Blennow^{1

2

24

25}

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg 417 11, Sweden.
² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 431 80, Sweden.
³ Neurology Department, Neurocode USA Inc, Bellingham, WA 98225, USA.
⁴ St George Hospital, South Eastern Sydney Local Health District, Sydney, New South Wales 2217, Australia.
⁵ Department of Neurology, University Hospital of North Norway, Tromsø 9038, Norway.
⁶ Department of Psychology, Faculty of Health Sciences, The Arctic University of Norway, Tromsø 9037, Norway.
⁷ Department of Neurology, Akershus University Hospital, Lørenskog 1478, Norway.
⁸ Learning and Leadership for Health Care Professionals at the Institute of Health and Care Science at Sahlgrenska Academy at University of Gothenburg, Gothenburg 417 11, Sweden.
⁹ Department of Clinical Neuroscience at the Institution of Neuroscience and Physiology at Sahlgrenska Academy at University of Gothenburg, Gothenburg 417 11, Sweden.
¹⁰ Clinical and Epidemiological Neuroscience Group (NeuroÈpia), Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus 43204, Spain.
¹¹ Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
¹² Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales 2050, Australia.
¹³ Bioventix Plc, Farnham, Surrey GU9 7SX, UK.
¹⁴ Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK.
¹⁵ UK Dementia Research Institute at UCL, London WC1N 3BG, UK.
¹⁶ Hong Kong Center for Neurodegenerative Diseases, Hong Kong 200020, China.
¹⁷ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53 792, USA.
¹⁸ University of Oslo, Institute for Clinical Medicine, Campus Ahus, Oslo 1478, Norway.
¹⁹ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
²⁰ Hospital del Mar Research Institute, Barcelona 08003, Spain.
²¹ Servei de Neurologia, Hospital del Mar, Barcelona 08003, Spain.
²² NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales 2006, Australia.
²³ Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales 2050, Australia.
²⁴ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris 75013, France.
²⁵ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei 230026, China.

PMID: 40574977
PMCID: PMC12198956
DOI: 10.1093/braincomms/fcaf221

The potential dual role of tau phosphorylation: plasma phosphorylated-tau217 in newborns and Alzheimer's disease

Fernando Gonzalez-Ortiz et al. Brain Commun. 2025.

. 2025 Jun 7;7(3):fcaf221.

doi: 10.1093/braincomms/fcaf221. eCollection 2025.

Authors

Affiliations

¹ Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg 417 11, Sweden.
² Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal 431 80, Sweden.
³ Neurology Department, Neurocode USA Inc, Bellingham, WA 98225, USA.
⁴ St George Hospital, South Eastern Sydney Local Health District, Sydney, New South Wales 2217, Australia.
⁵ Department of Neurology, University Hospital of North Norway, Tromsø 9038, Norway.
⁶ Department of Psychology, Faculty of Health Sciences, The Arctic University of Norway, Tromsø 9037, Norway.
⁷ Department of Neurology, Akershus University Hospital, Lørenskog 1478, Norway.
⁸ Learning and Leadership for Health Care Professionals at the Institute of Health and Care Science at Sahlgrenska Academy at University of Gothenburg, Gothenburg 417 11, Sweden.
⁹ Department of Clinical Neuroscience at the Institution of Neuroscience and Physiology at Sahlgrenska Academy at University of Gothenburg, Gothenburg 417 11, Sweden.
¹⁰ Clinical and Epidemiological Neuroscience Group (NeuroÈpia), Institut d'Investigació Sanitària Pere Virgili (IISPV), Reus 43204, Spain.
¹¹ Central Clinical School, Faculty of Medicine and Health, The University of Sydney, Sydney, New South Wales 2006, Australia.
¹² Department of Anaesthetics, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales 2050, Australia.
¹³ Bioventix Plc, Farnham, Surrey GU9 7SX, UK.
¹⁴ Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK.
¹⁵ UK Dementia Research Institute at UCL, London WC1N 3BG, UK.
¹⁶ Hong Kong Center for Neurodegenerative Diseases, Hong Kong 200020, China.
¹⁷ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53 792, USA.
¹⁸ University of Oslo, Institute for Clinical Medicine, Campus Ahus, Oslo 1478, Norway.
¹⁹ Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona 08005, Spain.
²⁰ Hospital del Mar Research Institute, Barcelona 08003, Spain.
²¹ Servei de Neurologia, Hospital del Mar, Barcelona 08003, Spain.
²² NHMRC Clinical Trials Centre, The University of Sydney, Sydney, New South Wales 2006, Australia.
²³ Institute of Academic Surgery, Royal Prince Alfred Hospital, Sydney Local Health District, Sydney, New South Wales 2050, Australia.
²⁴ Paris Brain Institute, ICM, Pitié-Salpêtrière Hospital, Sorbonne University, Paris 75013, France.
²⁵ Neurodegenerative Disorder Research Center, Division of Life Sciences and Medicine, and Department of Neurology, Institute on Aging and Brain Disorders, University of Science and Technology of China and First Affiliated Hospital of USTC, Hefei 230026, China.

PMID: 40574977
PMCID: PMC12198956
DOI: 10.1093/braincomms/fcaf221

Abstract

Tau phosphorylation plays an important role in brain physiology and pathology. During foetal development, it supports microtubule dynamics and neuroplasticity, whereas in Alzheimer's disease (AD), it drives pathological tau aggregation and tangle formation. In this multicentre study (n = 462), we measured plasma phosphorylated-tau217 in healthy newborns, premature infants, patients with AD and healthy controls across various age groups. Plasma phosphorylated-tau217 levels were significantly higher in newborns compared to healthy individuals of any age group and even exceeded levels observed in patients with AD. In newborns, plasma phosphorylated-tau217 levels inversely correlated with perinatal factors such as gestational age. Longitudinal analysis of preterm infants demonstrated a decline in serum phosphorylated-tau217 levels over the first months of life, approaching levels observed in young adults. In contrast, elevated plasma phosphorylated-tau217 in older individuals was associated with AD pathology. Our findings corroborate the crucial role of tau phosphorylation in early brain development. However, in AD, tau phosphorylation transitions into a pathological mechanism. The high levels of blood-based phosphorylated-tau217 observed at birth and subsequent clearance might indicate distinct regulatory mechanisms that prevent tau aggregation in early life. Further studies are needed to explore the shared mechanisms of tau phosphorylation in newborns and AD.

Keywords: Alzheimer’s disease; newborns; phosphorylated tau; plasma biomarkers.

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Conflict of interest statement

M.T. and P.H. are employees of Bioventix. HZ has served at scientific advisory boards and/or as a consultant for AbbVie Inc, Acumen, Alector, Alzinova, ALZpath, Amylyx, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Enigma, LabCorp, Merry Life, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Quanterix, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics and Wave, has given lectures sponsored by Alzecure, BioArctic, Biogen, Cellectricon, Fujirebio, Lilly, Novo Nordisk, Roche and WebMD 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). K.B. has served as a consultant and at advisory boards for AbbVie, AC Immune, ALZpath, AriBio, Beckman-Coulter, BioArctic, Biogen, Eisai, Lilly, Moleac Pte. Ltd, Neurimmune, Novartis, Ono Pharma, Prothena, Quanterix, Roche Diagnostics, Sanofi and Siemens Healthineers; has served at data monitoring committees for Julius Clinical and Novartis; has given lectures, produced educational materials and participated in educational programmes for AC Immune, Biogen, Celdara Medical, Eisai and Roche Diagnostics; and is a co-founder of Brain Biomarker Solutions in Gothenburg AB, which is a part of the GU Ventures Incubator Program, outside the work presented in this paper. M.S.-C. has served as a consultant and at advisory boards for Roche Diagnostics International Ltd and Grifols S.L., has given lectures in symposia sponsored by Roche Diagnostics and Roche Farma, S.A. and was granted with a project funded by Roche Diagnostics International Ltd; payments were made to the institution (Barcelona Beta Research Center). B.-E.K. has served as a consultant for Biogen and advisory board for Eisai. T.F. has served as a consultant and at the advisory boards for Biogen, Novo Nordisk, Eli Lilly and Roche. The other authors declare no competing interest.

Figures

**Figure 2**
**Levels of plasma p-tau217 in healthy controls, Alzheimer’s disease and newborns. A** shows a comparison of plasma p-tau217 concentrations (pg/mL) among four groups: controls (n = 56), Alzheimer’s disease cohort (n = 163), newborns cohort-1 (n = 55) and newborns cohort-2 (n = 106). Group differences were examined using the Mann–Whitney test (two categories) or the Kruskal–Wallis test with Dunn’s multiple comparisons (three groups). In each box plot, the horizontal bar on top of the coloured area shows the 75% percentile, the middle bar depicts the median, and the lower bar shows the 25% percentile. Values that are above the 75% percentile and below the 25% percentile are shown outside the coloured area. Each individual data point represents the plasma p-tau217 concentration measured from a single participant within the respective group. (B) Z-score-transformed plasma p-tau217 concentrations are shown for the control group (cohort-3), the Alzheimer’s disease group (cohort-3) and newborns (cohort-1 and cohort-2). Group differences in this panel were also assessed using the Kruskal–Wallis test with Dunn’s multiple comparisons test.

**Figure 3**
**Longitudinal trajectories of serum p-tau217 in preterm infants < 28 weeks gestational age at birth.** Spaghetti plot showing the longitudinal changes in serum p-tau217 levels in individual preterm infants over time (n = 14), measured in postnatal weeks. Each curve represents a single patient, with dots marking serum p-tau217 levels at specific time points.

See this image and copyright information in PMC

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The potential dual role of tau phosphorylation: plasma phosphorylated-tau217 in newborns and Alzheimer's disease

Affiliations

The potential dual role of tau phosphorylation: plasma phosphorylated-tau217 in newborns and Alzheimer's disease

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

LinkOut - more resources

Full Text Sources