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Glial fibrillary acidic protein (GFAP), myelin basic protein (MBP), neurofilament light chain (NFL), tau and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) are five neuroglial proteins that are used as CSF or blood biomarkers of tissue damage in the nervous system. There is incomplete knowledge of how the concentration of these proteins differs between anatomical regions in the CNS as previous studies have focused on gene expression or non-quantitative protein analyses, limiting the interpretability of these biomarkers. The purpose of this study was to create a map of the tissue content of these proteins in different regions of the CNS. The concentrations of the investigated proteins were determined with ELISA in post mortem tissue homogenates from 17 selected anatomical regions in the CNS from ten deceased donors aged 24 to 50 years. When appropriate, the protein concentrations were adjusted for post-mortem interval. In total, 168 tissue samples were analysed. There was a substantial variation in the concentrations of GFAP, MBP, NFL, tau and UCHL1 between different CNS regions. Highly myelinated areas of the CNS had tenfold higher MBP concentration than cerebral cortex, whereas tau showed an inverse pattern. GFAP, NFL and tau displayed an anteroposterior gradient in cerebral white matter. The cerebellum had low concentrations of all the investigated proteins. In conclusion, the tissue concentrations of GFAP, MBP, NFL, tau and UCHL1 were determined throughout the CNS. This information can be used as a reference when interpreting circulating levels of these biomarkers in relation to the extent and localisation of CNS-damaging processes.

Objective: To determine the temporal profiles of glial fibrillary acidic protein (GFAP), neurofilament light (NFL), total tau (t-tau), and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) in plasma the first week after acute ischemic stroke, and identify the optimal time points for assessing infarct volume by these biomarkers.

Patients & Methods: In this cohort study, biomarker plasma concentrations were determined daily over the first week and at 90 days after symptom onset in patients with acute ischemic stroke. A brain MRI was performed on day three. Temporal variations in biomarker levels were analyzed using linear mixed-effects models, and optimal time points for infarct volume correlation were identified with continuous Pearson analysis.

Results: 38 patients with a median age of 78 (IQR 72-86) and mean infarct volume of 5.5 (IQR 1.6-17) cm³ were included. We identified three distinct temporal patterns: (1) a parabolic trajectory of GFAP, reaching zenith after three days, (2) a consistent increase in NFL throughout the week, and (3) an initial surge in t-tau and UCHL1 levels, stabilizing by day three. The optimal time point for infarct volume correlation occurred at 119 h for GFAP (r=0.94, 95% CI: [0.84-0.98]), 144 h for NFL (r=0.78, [0.47, 0.92]), 122 h for t-tau (r=0.82, [0.56, 0.93]) and 113 h for UCHL1 (r=0.83, [0.60, 0.93]).

Conclusion: This high-resolution serial sampling of plasma GFAP, NFL, t-tau, and UCHL1 the first week after acute ischemic stroke identified three distinct temporal profiles. These biomarkers provided the most accurate infarct volume assessment 4-6 days after symptom onset.

Introduction: Transcatheter aortic valve implantation (TAVI) is associated with a high incidence of new silent brain infarcts (SBIs) on postprocedural neuroimaging. A venous blood sample reflecting neuronal damage following TAVI could help identify patients with potential SBIs. We aimed to investigate if a biochemical marker of neuronal injury, neurofilament light chain (NFL), is elevated after TAVI.

Methods: In this observational study, NFL was measured in plasma from 31 patients before and after TAVI. Multivariable regression analysis was performed to investigate any effect of clinical- and procedure-related factors on differences in NFL levels before and after TAVI.

Results: Samples were collected 41 (14–81) days before and 44 (35–59) days after TAVI, median (interquartile range). Median age was 81 (77–84) years, and 35% were female. No patient had any overt procedure-related neurological complications. The geometric mean (95% confidence interval) of the NFL concentration was 30 (25–36) pg/mL before TAVI and 48 (39–61) pg/mL, after TAVI, p <0.001. None of the included variables in the multiple linear regression model were statistically significantly associated with the difference in levels before and after TAVI.

Conclusions: NFL levels in plasma were higher after TAVI as compared with levels before, with a mean increase of 60% (18 pg/mL). Further studies including neuroimaging and cognitive outcomes are needed to understand the potential value of measuring NFL in relation to TAVI.

BACKGROUND: Atrial fibrillation (AF) is associated with stroke and MRI features of cerebral tissue damage but its impact on levels of serum neurofilament light chain (sNFL), an established biochemical marker of neuroaxonal damage, is unknown.

METHODS AND RESULTS: In this observational study, sNFL was analyzed in 280 patients with AF and 280 controls without AF matched for age, sex, and diabetes status within the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial. None of the patients had a history of previous stroke or transient ischemic attack. Patients with a diagnosis of AF were divided into two groups based on if they were in AF rhythm at the time of blood sampling (AF ECG+, n=74), or not (AF ECG-, n=206). Multiple linear regression analysis was performed to adjust for clinical risk factors. In patients with AF, the levels of sNFL were 15% (AF ECG+) and 10% (AF ECG-) higher than in the control group after adjustment for clinical risk factors, P=0.047 and 0.04, respectively. There was no association between anticoagulation treatment and sNFL levels.

CONCLUSIONS: sNFL was elevated in patients with AF compared with matched controls without AF. Ongoing AF rhythm was associated with even higher levels of sNFL than in patients with a diagnosis of AF but currently not in AF rhythm. Anticoagulation treatment did not affect sNFL levels.