Alzheimer's disease marker phospho-tau181 is not elevated in the first year after moderate-to-severe TBI

BACKGROUND: Traumatic 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. METHODS: Plasma 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. RESULTS: Plasma 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. CONCLUSIONS: Plasma 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

Passing Figures: Fashion and the Formation of Modernist Identity in the American Novel

This dissertation considers the way in which the figure of fashion expands and complicates the field of literary modernism. My project treats "fashion" as more than just clothing and other bodily adornment, broadening it to include certain spaces, locations, and objects organized by social hierarchies of performance and display. I focus on the way in which characters--often in the texts of authors on the margins of mainstream modernism--use fashionable dress and the manipulation of social spaces to defy constraining social positions. I argue that fashionable expression allows characters to revise personal history and represent a self in opposition to externally imposed perceptions of identity.The readings of fashionable "moments" I consider show how fashion, like the modernist aesthetic itself, allows authors to fragment and remake conceptions of self and persona, meaning and value, and past and present, all categories scholars now argue were at the heart of the aesthetics of modernism. In chapters on Theodore Dreiser, Edith Wharton, Nella Larsen, and William Faulkner, I explore the production of womanhood as anti-modern, the generation of personhood through new relations to things, the relations of the signs of race to the more general fashion system, and the relation between the domestic, modernity, and the American South. Examining texts through the lens of fashion reveals the ways in which modernist moments are produced by characters, subjects and authors often considered to be outside the boundaries of the modernist movement through an engagement with concepts of the fashionable, and the remaking of the self it allows. Building on the history of scholarship on modernist aesthetics, and on recent work on the role fashion played in the production and growth of the spirit of modernity, I show how, at the fringes of the American aesthetic, the frictions that brought literature in contact with the fashion system allow us to rethink the history of the early twentieth century

Axonal marker neurofilament light predicts long-term outcomes and progressive neurodegeneration after traumatic brain injury

Axonal injury is a key determinant of long-term outcomes after traumatic brain injury (TBI) but has been difficult to measure clinically. Fluid biomarker assays can now sensitively quantify neuronal proteins in blood. Axonal components such as neurofilament light (NfL) potentially provide a diagnostic measure of injury. In the multicenter BIO-AX-TBI study of moderate-severe TBI, we investigated relationships between fluid biomarkers, advanced neuroimaging, and clinical outcomes. Cerebral microdialysis was used to assess biomarker concentrations in brain extracellular fluid aligned with plasma measurement. An experimental injury model was used to validate biomarkers against histopathology. Plasma NfL increased after TBI, peaking at 10 days to 6 weeks but remaining abnormal at 1 year. Concentrations were around 10 times higher early after TBI than in controls (patients with extracranial injuries). NfL concentrations correlated with diffusion MRI measures of axonal injury and predicted white matter neurodegeneration. Plasma TAU predicted early gray matter atrophy. NfL was the strongest predictor of functional outcomes at 1 year. Cerebral microdialysis showed that NfL concentrations in plasma and brain extracellular fluid were highly correlated. An experimental injury model confirmed a dose-response relationship of histopathologically defined axonal injury to plasma NfL. In conclusion, plasma NfL provides a sensitive and clinically meaningful measure of axonal injury produced by TBI. This reflects the extent of underlying damage, validated using advanced MRI, cerebral microdialysis, and an experimental model. The results support the incorporation of NfL sampling subacutely after injury into clinical practice to assist with the diagnosis of axonal injury and to improve prognostication.</p