Nature Communications (Apr 2024)
Plasma brain-derived tau is an amyloid-associated neurodegeneration biomarker in Alzheimer’s disease
- Fernando Gonzalez-Ortiz,
- Bjørn-Eivind Kirsebom,
- José Contador,
- Jordan E. Tanley,
- Per Selnes,
- Berglind Gísladóttir,
- Lene Pålhaugen,
- Mathilde Suhr Hemminghyth,
- Jonas Jarholm,
- Ragnhild Skogseth,
- Geir Bråthen,
- Gøril Grøndtvedt,
- Atle Bjørnerud,
- Sandra Tecelao,
- Knut Waterloo,
- Dag Aarsland,
- Aida Fernández-Lebrero,
- Greta García-Escobar,
- Irene Navalpotro-Gómez,
- Michael Turton,
- Agnes Hesthamar,
- Przemyslaw R. Kac,
- Johanna Nilsson,
- Jose Luchsinger,
- Kathleen M. Hayden,
- Peter Harrison,
- Albert Puig-Pijoan,
- Henrik Zetterberg,
- Timothy M. Hughes,
- Marc Suárez-Calvet,
- Thomas K. Karikari,
- Tormod Fladby,
- Kaj Blennow
Affiliations
- Fernando Gonzalez-Ortiz
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg
- Bjørn-Eivind Kirsebom
- Department of Neurology, University Hospital of North Norway
- José Contador
- Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation
- Jordan E. Tanley
- Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine
- Per Selnes
- Department of Neurology, Akershus University Hospital
- Berglind Gísladóttir
- Department of Neurology, Akershus University Hospital
- Lene Pålhaugen
- Department of Neurology, Akershus University Hospital
- Mathilde Suhr Hemminghyth
- Research Group for Age-Related Medicine, Haugesund Hospital
- Jonas Jarholm
- Department of Neurology, Akershus University Hospital
- Ragnhild Skogseth
- Department of Geriatric Medicine, Haraldsplass Deaconess Hospital
- Geir Bråthen
- Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim
- Gøril Grøndtvedt
- Department of Neurology and Clinical Neurophysiology, University Hospital of Trondheim
- Atle Bjørnerud
- Department of Physics, University of Oslo
- Sandra Tecelao
- Department of Neurology, Akershus University Hospital
- Knut Waterloo
- Department of Neurology, University Hospital of North Norway
- Dag Aarsland
- Department of Old Age Psychiatry. Institute of psychiatry, Psychology and Neuroscience King’s College London
- Aida Fernández-Lebrero
- Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation
- Greta García-Escobar
- Hospital del Mar Research Institute
- Irene Navalpotro-Gómez
- Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation
- Michael Turton
- Bioventix Plc
- Agnes Hesthamar
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg
- Przemyslaw R. Kac
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg
- Johanna Nilsson
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg
- Jose Luchsinger
- Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine
- Kathleen M. Hayden
- Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine
- Peter Harrison
- Bioventix Plc
- Albert Puig-Pijoan
- Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation
- Henrik Zetterberg
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg
- Timothy M. Hughes
- Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine
- Marc Suárez-Calvet
- Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation
- Thomas K. Karikari
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg
- Tormod Fladby
- Institute of Clinical Medicine, Campus Ahus, University of Oslo
- Kaj Blennow
- Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, the Sahlgrenska Academy at the University of Gothenburg
- DOI
- https://doi.org/10.1038/s41467-024-47286-5
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 1 – 13
Abstract
Abstract Staging amyloid-beta (Aβ) pathophysiology according to the intensity of neurodegeneration could identify individuals at risk for cognitive decline in Alzheimer’s disease (AD). In blood, phosphorylated tau (p-tau) associates with Aβ pathophysiology but an AD-type neurodegeneration biomarker has been lacking. In this multicenter study (n = 1076), we show that brain-derived tau (BD-tau) in blood increases according to concomitant Aβ (“A”) and neurodegeneration (“N”) abnormalities (determined using cerebrospinal fluid biomarkers); We used blood-based A/N biomarkers to profile the participants in this study; individuals with blood-based p-tau+/BD-tau+ profiles had the fastest cognitive decline and atrophy rates, irrespective of the baseline cognitive status. Furthermore, BD-tau showed no or much weaker correlations with age, renal function, other comorbidities/risk factors and self-identified race/ethnicity, compared with other blood biomarkers. Here we show that blood-based BD-tau is a biomarker for identifying Aβ-positive individuals at risk of short-term cognitive decline and atrophy, with implications for clinical trials and implementation of anti-Aβ therapies.
