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Sökning: WFRF:(Janelidze S) > (2020-2024) > Ultra-high field im...

  • Van Egroo, M.Harvard Medical School,Massachusetts General Hospital,Yukioka Hospital (författare)

Ultra-high field imaging, plasma markers and autopsy data uncover a specific rostral locus coeruleus vulnerability to hyperphosphorylated tau

  • Artikel/kapitelEngelska2023

Förlag, utgivningsår, omfång ...

  • 2023

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/326260
  • https://gup.ub.gu.se/publication/326260URI
  • https://doi.org/10.1038/s41380-023-02041-yDOI
  • https://lup.lub.lu.se/record/2ef30f6e-7671-45c1-82ed-da36bf925c33URI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Autopsy data indicate that the locus coeruleus (LC) is one of the first sites in the brain to accumulate hyperphosphorylated tau pathology, with the rostral part possibly being more vulnerable in the earlier stages of the disease. Taking advantage of recent developments in ultra-high field (7 T) imaging, we investigated whether imaging measures of the LC also reveal a specific anatomic correlation with tau using novel plasma biomarkers of different species of hyperphosphorylated tau, how early in adulthood these associations can be detected and if are associated with worse cognitive performance. To validate the anatomic correlations, we tested if a rostro-caudal gradient in tau pathology is also detected at autopsy in data from the Rush Memory and Aging Project (MAP). We found that higher plasma measures of phosphorylated tau, in particular ptau(231), correlated negatively with dorso-rostral LC integrity, whereas correlations for neurodegenerative plasma markers (neurofilament light, total tau) were scattered throughout the LC including middle to caudal sections. In contrast, the plasma A beta(42/40) ratio, associated with brain amyloidosis, did not correlate with LC integrity. These findings were specific to the rostral LC and not observed when using the entire LC or the hippocampus. Furthermore, in the MAP data, we observed higher rostral than caudal tangle density in the LC, independent of the disease stage. The in vivo LC-phosphorylated tau correlations became significant from midlife, with the earliest effect for ptau(231), starting at about age 55. Finally, interactions between lower rostral LC integrity and higher ptau(231) concentrations predicted lower cognitive performance. Together, these findings demonstrate a specific rostral vulnerability to early phosphorylated tau species that can be detected with dedicated magnetic resonance imaging measures, highlighting the promise of LC imaging as an early marker of AD-related processes.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Riphagen, J. M.Harvard Medical School,Massachusetts General Hospital (författare)
  • 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,Stavanger University Hospital,Sahlgrenska Academy(Swepub:gu)xashtn (författare)
  • Janelidze, ShorenaLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups(Swepub:lu)nkir-sje (författare)
  • Sperling, R. A.Massachusetts General Hospital,Harvard Medical School,Brigham and Women's Hospital / Harvard Medical School (författare)
  • Johnson, K. A.Harvard Medical School,Massachusetts General Hospital (författare)
  • Yang, H. S.Massachusetts General Hospital,Harvard Medical School,Brigham and Women's Hospital / Harvard Medical School (författare)
  • Bennett, D. A.Rush Alzheimer's Disease Center (författare)
  • 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 University Hospital,Sahlgrenska Academy(Swepub:lu)med-kbw (författare)
  • Hansson, OskarLund University,Lunds universitet,Klinisk minnesforskning,Forskargrupper vid Lunds universitet,Clinical Memory Research,Lund University Research Groups,Skåne University Hospital(Swepub:lu)mphy-ohn (författare)
  • 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 University Hospital,Sahlgrenska Academy,University College London(Swepub:lu)med-hiz (författare)
  • Jacobs, H. I. L.Massachusetts General Hospital,Yukioka Hospital,Harvard Medical School (författare)
  • Harvard Medical SchoolMassachusetts General Hospital (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Molecular Psychiatry28:6, s. 2412-24221359-4184

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