New Brain Tau Blood Biomarker Offers 'Troponin for the Brain'

A new blood biomarker—brain-derived tau (BD-tau)—is able to track the extent of brain injury over time after an ischaemic stroke, as reported by researchers from Ludwig Maximilian University (LMU; Munich, Germany) and international partners. This novel biomarker may also be predictive of patients’ functional outcomes months or even years after their stroke, potentially enabling the detection of differences associated with successful vessel reopening as well as the effect of a drug tested in a clinical trial. These data and resulting conclusions have been published by co-first authors Naomi Vlegels and Nicoló Luca Knuth—both of LMU—in the journal Science Translational Medicine. According to the researchers, in the acute phase of ischaemic stroke, medical imaging modalities such as computed tomography (CT) or magnetic resonance (MR) scans typically only provide ‘point-in-time’ information. Additionally, repeated scans are often logistically demanding or not feasible, and imaging measures typically only reflect later recovery to a limited extent. While acute injury to the heart or kidneys can often be monitored with blood tests, the brain has lacked such a marker to date, the researchers also aver. “In stroke care, we currently face the problem that we cannot continuously track how brain injury evolves over time—and this limits our treatment decisions,” explained Steffen Tiedt (Institute for Stroke and Dementia Research, Munich, Germany). To address this need, Tiedt initiated a study at LMU Klinikum in 2013 with the goal of developing a reliable blood test that could continuously reflect brain injury and make treatment effects measurable. His team subsequently identified BD-tau as a blood biomarker that may be able to do exactly that by capturing tau protein originating from the central nervous system. In the study cohort, BD-tau was measured repeatedly from hospital admission through day seven. The findings were additionally validated in two independent, multicentre cohorts, including a biomarker-based analysis within a phase-three clinical trial. In total, data from more than 1,200 stroke patients were included in these analyses. Tiedt and colleagues found that blood levels of BD-tau reflected the extent of brain injury, with early levels measured within hours after symptom onset being associated with the initial degree of damage and proving to be predictive of final infarct size. BD-tau also captured disease dynamics, as larger increases during the first 24–48 hours were linked to infarct growth, and elevated levels were observed in complications like recurrent events too. Moreover, BD-tau was found to be a “strong predictor” of recovery, forecasting functional outcomes at 90 days and beyond—doing so at least as well as, or better than, other blood biomarkers and even imaging-based infarct volumes. BD-tau also revealed insights on treatment effects. After a thrombectomy procedure, levels of the biomarker rose by a smaller amount when the vessel was fully reopened. Furthermore, in a randomised study, the rise in BD-tau was markedly smaller with the neuroprotectant nerinetide as compared to with placebo. “We don’t just need a picture from the beginning of a stroke, we need a way to follow the course of brain injury over time,” Tiedt added. “BD-tau could become a kind of ‘troponin for the brain’—an objective blood marker that makes progression and treatment effects measurable.” The researchers emphasise that more studies are needed to, for example, define reference ranges and thresholds, and enable faster measurement of BD-tau in the future—ideally making it a point-of-care test further down the line. They believe that, in the long term, such a blood test could help clinicians monitor disease trajectories more closely, detect complications earlier, and evaluate new therapies more efficiently in clinical trials. In addition, the researchers note that BD-tau could help objectively and rapidly assess brain injury in other neurological diseases.