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- Graham, N., et al.
(författare)
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Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI
- 2024
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Ingår i: Journal of Neurology Neurosurgery and Psychiatry. - 0022-3050. ; 95:4, s. 356-359
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundTraumatic brain injury (TBI) is associated with the tauopathies Alzheimer's disease and chronic traumatic encephalopathy. Advanced immunoassays show significant elevations in plasma total tau (t-tau) early post-TBI, but concentrations subsequently normalise rapidly. Tau phosphorylated at serine-181 (p-tau181) is a well-validated Alzheimer's disease marker that could potentially seed progressive neurodegeneration. We tested whether post-traumatic p-tau181 concentrations are elevated and relate to progressive brain atrophy.MethodsPlasma p-tau181 and other post-traumatic biomarkers, including total-tau (t-tau), neurofilament light (NfL), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), were assessed after moderate-to-severe TBI in the BIO-AX-TBI cohort (first sample mean 2.7 days, second sample within 10 days, then 6 weeks, 6 months and 12 months, n=42). Brain atrophy rates were assessed in aligned serial MRI (n=40). Concentrations were compared patients with and without Alzheimer's disease, with healthy controls.ResultsPlasma p-tau181 concentrations were significantly raised in patients with Alzheimer's disease but not after TBI, where concentrations were non-elevated, and remained stable over one year. P-tau181 after TBI was not predictive of brain atrophy rates in either grey or white matter. In contrast, substantial trauma-associated elevations in t-tau, NfL, GFAP and UCH-L1 were seen, with concentrations of NfL and t-tau predictive of brain atrophy rates.ConclusionsPlasma p-tau181 is not significantly elevated during the first year after moderate-to-severe TBI and levels do not relate to neuroimaging measures of neurodegeneration.
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| 2. |
- Leckey, Claire A, et al.
(författare)
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CSF neurofilament light chain profiling and quantitation in neurological diseases.
- 2024
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Ingår i: Brain communications. - 2632-1297. ; 6:3
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Tidskriftsartikel (refereegranskat)abstract
- Neurofilament light chain is an established marker of neuroaxonal injury that is elevated in CSF and blood across various neurological diseases. It is increasingly used in clinical practice to aid diagnosis and monitor progression and as an outcome measure to assess safety and efficacy of disease-modifying therapies across the clinical translational neuroscience field. Quantitative methods for neurofilament light chain in human biofluids have relied on immunoassays, which have limited capacity to describe the structure of the protein in CSF and how this might vary in different neurodegenerative diseases. In this study, we characterized and quantified neurofilament light chain species in CSF across neurodegenerative and neuroinflammatory diseases and healthy controls using targeted mass spectrometry. We show that the quantitative immunoprecipitation-tandem mass spectrometry method developed in this study strongly correlates to single-molecule array measurements in CSF across the broad spectrum of neurodegenerative diseases and was replicable across mass spectrometry methods and centres. In summary, we have created an accurate and cost-effective assay for measuring a key biomarker in translational neuroscience research and clinical practice, which can be easily multiplexed and translated into clinical laboratories for the screening and monitoring of neurodegenerative disease or acute brain injury.
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