A specific and accurate blood test for acute brain injury could help monitor infarct growth in ischemic stroke and serve as a surrogate end point in clinical trials. Using a single-molecule detection assay, we assessed plasma brain-derived tau (BD-tau), a marker selectively quantifying tau protein from the central nervous system, in a prospective cohort of 502 patients with acute ischemic stroke with serial blood sampling from admission to day 7. Higher BD-tau concentrations at admission were associated with more extensive early brain injury on computed tomography and predicted larger final infarct volumes. BD-tau increases from admission to day 2 were related to infarct growth. BD-tau concentrations rose until day 7 and were higher in patients with secondary events, including recurrent stroke. After thrombectomy, the rise of BD-tau was smaller in patients with complete versus incomplete recanalization. BD-tau outperformed other blood markers and imaging metrics in predicting 90-day functional outcome across infarct size strata and time points. In an independent multicenter prospective cohort ( N = 519), BD-tau showed higher performance than magnetic resonance imaging–derived final infarct volume in predicting functional outcomes at 3, 12, and 36 months. In the biomarker substudy of a phase 3 trial assessing nerinetide in patients with ischemic stroke ( N = 193), BD-tau showed predictive performance comparable to the other cohorts, mediated the relationship between recanalization and functional outcome, and showed a 49% smaller increase in the nerinetide group versus placebo. Overall, plasma BD-tau tracked ischemic brain injury over time, outperformed other biomarkers in predicting functional outcomes, and identified possible treatment responses.

Hepatic iron overload can cause severe organ damage; therefore, an early diagnosis and the identification of potential risk factors is crucial. We aimed to investigate the sex-specific distribution of hepatic iron content (HIC) in a population-based cohort and identify relevant associated factors from a panel of markers. We analyzed N = 353 participants from a cross-sectional sample (KORA FF4) who underwent whole-body magnetic resonance imaging. HIC was assessed by single-voxel spectroscopy with a high-speed T2-corrected multi-echo technique. A large panel of markers, including anthropometric, genetic, and laboratory values, as well as behavioral risk factors were assessed. Relevant factors associated with HIC were identified by variable selection based on LASSO regression with bootstrap resampling. HIC in the study sample (mean age at examination: 56.0 years, 58.4% men) was significantly lower in women (mean ± SD: 39.2 ± 4.1 s⁻¹) than in men (41.8 ± 4.7 s⁻¹, p < 0.001). Relevant factors associated with HIC were HbA1c as well as prediabetes for men and visceral adipose tissue as well as age for women. Hepatic fat, alcohol consumption, and genetic risk score for iron levels were associated with HIC in both sexes. In conclusion, there are sex-specific associations of HIC with markers of body composition, glucose metabolism, and alcohol consumption.

Iron-related disorders of the liver can result in serious health conditions, such as liver cirrhosis. Evidence on the role of modifiable lifestyle factors like nutrition in liver iron storage is lacking. Thus, we aimed to assess the association of habitual diet with liver iron content (LIC). We investigated 303 participants from the population-based KORA-MRI study who underwent whole-body magnetic resonance imaging (MRI). Dietary habits were evaluated using repeated 24 h food lists and a food frequency questionnaire. Sex-stratified multiple linear regression models were applied to quantify the association between nutrition variables of interest and LIC, adjusting for liver fat content (LFC), energy intake, and age. Mean age of participants was 56.4 ± 9.0 years and 44.2% were female. Mean LIC was 1.23 ± 0.12 mg/g dry weight, with higher values in men than in women (1.26 ± 0.13 and 1.20 ± 0.10 mg/g, p < 0.001). Alcohol intake was positively associated with LIC (men: β = 1.94; women: β = 4.98, p-values < 0.03). Significant negative associations with LIC were found for fiber (β = −5.61, p < 0.001) and potassium (β = −0.058, p = 0.034) for female participants only. Furthermore, LIC was highly correlated with liver fat content in both sexes. Our findings suggests that there are sex-specific associations of habitual dietary intake and LIC. Alcohol, fiber, and potassium may play a considerable role in liver iron metabolism.