Plasma N-terminal containing tau fragments (NTA-tau): a biomarker of tau deposition in Alzheimer's Disease.

Autor: Lantero-Rodriguez J; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden. juan.rodriguez.2@gu.se., Salvadó G; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Snellman A; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden.; Turku PET Centre, University of Turku, Turku University Hospital, Turku, Finland., Montoliu-Gaya L; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden., Brum WS; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden.; Graduate Program in Biological Sciences: Biochemistry, Universidade Federal Do Rio Grande Do Sul (UFRGS), Porto Alegre, Brazil., Benedet AL; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden., Mattsson-Carlgren N; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Department of Neurology, Skåne University Hospital, Lund, Sweden.; Wallenberg Center for Molecular Medicine, Lund University, Lund, Sweden., Tideman P; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Memory Clinic, Skåne University Hospital, 20502, Malmö, Sweden., Janelidze S; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Palmqvist S; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden., Stomrud E; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden.; Memory Clinic, Skåne University Hospital, 20502, Malmö, Sweden., Ashton NJ; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden.; Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden.; Department of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King's College London, London, UK.; NIHR Biomedical Research Centre for Mental Health & Biomedical Research Unit for Dementia at South London & Maudsley NHS Foundation, London, UK., Zetterberg H; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden.; Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London, UK.; UK Dementia Research Institute, University College London, London, UK.; Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China.; Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA., Blennow K; Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, House V3/SU, 43180, Mölndal, Sweden.; Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, Mölndal, Sweden., Hansson O; Clinical Memory Research Unit, Department of Clinical Sciences Malmö, Lund University, Lund, Sweden. oskar.hansson@med.lu.se.; Memory Clinic, Skåne University Hospital, 20502, Malmö, Sweden. oskar.hansson@med.lu.se.
Jazyk: angličtina
Zdroj: Molecular neurodegeneration [Mol Neurodegener] 2024 Feb 17; Vol. 19 (1), pp. 19. Date of Electronic Publication: 2024 Feb 17.
DOI: 10.1186/s13024-024-00707-x
Abstrakt: Background: Novel phosphorylated-tau (p-tau) blood biomarkers (e.g., p-tau181, p-tau217 or p-tau231), are highly specific for Alzheimer's disease (AD), and can track amyloid-β (Aβ) and tau pathology. However, because these biomarkers are strongly associated with the emergence of Aβ pathology, it is difficult to determine the contribution of insoluble tau aggregates to the plasma p-tau signal in blood. Therefore, there remains a need for a biomarker capable of specifically tracking insoluble tau accumulation in brain.
Methods: NTA is a novel ultrasensitive assay targeting N-terminal containing tau fragments (NTA-tau) in cerebrospinal fluid (CSF) and plasma, which is elevated in AD. Using two well-characterized research cohorts (BioFINDER-2, n = 1,294, and BioFINDER-1, n = 932), we investigated the association between plasma NTA-tau levels and disease progression in AD, including tau accumulation, brain atrophy and cognitive decline.
Results: We demonstrate that plasma NTA-tau increases across the AD continuum¸ especially during late stages, and displays a moderate-to-strong association with tau-PET (β = 0.54, p < 0.001) in Aβ-positive participants, while weak with Aβ-PET (β = 0.28, p < 0.001). Unlike plasma p-tau181, GFAP, NfL and t-tau, tau pathology determined with tau-PET is the most prominent contributor to NTA-tau variance (52.5% of total R 2 ), while having very low contribution from Aβ pathology measured with CSF Aβ42/40 (4.3%). High baseline NTA-tau levels are predictive of tau-PET accumulation (R 2  = 0.27), steeper atrophy (R 2  ≥ 0.18) and steeper cognitive decline (R 2  ≥ 0.27) in participants within the AD continuum. Plasma NTA-tau levels significantly increase over time in Aβ positive cognitively unimpaired (β std  = 0.16) and impaired (β std  = 0.18) at baseline compared to their Aβ negative counterparts. Finally, longitudinal increases in plasma NTA-tau levels were associated with steeper longitudinal decreases in cortical thickness (R 2  = 0.21) and cognition (R 2  = 0.20).
Conclusion: Our results indicate that plasma NTA-tau levels increase across the AD continuum, especially during mid-to-late AD stages, and it is closely associated with in vivo tau tangle deposition in AD and its downstream effects. Moreover, this novel biomarker has potential as a cost-effective and easily accessible tool for monitoring disease progression and cognitive decline in clinical settings, and as an outcome measure in clinical trials which also need to assess the downstream effects of successful Aβ removal.
(© 2024. The Author(s).)
Databáze: MEDLINE
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