• Neil Graham, Karl Zimmerman, Amanda J Heslegrave, Ashvini Keshavan, Federico Moro, Samia Abed-Maillard, Adriano Bernini, Vincent Dunet, Elena Garbero, Giovanni Nattino, Arturo Chieregato, Enrico Fainardi, Camelia Baciu, Primoz Gradisek, Sandra Magnoni, Mauro Oddo, Guido Bertolini, Jonathan M Schott, Henrik Zetterberg, and David Sharp.
• Brain Sciences, Imperial College London, London, UK.
• J. Neurol. Neurosurg. Psychiatr. 2024 Mar 13; 95 (4): 356359356-359.

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.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.

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