Plasma Desmoplakin as a Novel Biomarker for Early-Onset Susceptibility and Prognostic Stratification in Young Intracerebral Hemorrhage.

Assessment of Brain-Specific and Neuroendocrine Biomarkers for Intracerebral Hemorrhage Diagnosis: A Prospective Cohort Study

Background and Purpose The timing of diagnosis is a critical factor that significantly impacts medical treatment and patient outcomes in individuals with intracerebral hemorrhage (ICH). The study primarily aimed to evaluate the diagnostic potential of four brain-specific biomarkers, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), tau, and ubiquitin C-terminal hydrolase-L1 (UCH-L1) to differentiate CT-confirmed ICH patients from healthy controls. Secondary aims included comparing results between younger (18-59 years) and older (≥60 years) ICH patients and exploring neuroendocrine hormone levels (adrenocorticotropic hormone [ACTH], agouti-related peptide [AgRP], ciliary neurotrophic factor [CNTF], and growth hormone [GH]) as potential diagnostic tools. Methods Serum samples were collected from consecutive adult patients with CT-confirmed ICH diagnoses on days 1 (first 24 hours), 2, 3, 7, and 14 for biomarker analyses in a pilot study. A total of 71 patients and 30 healthy controls were included in the analysis. Results Serum concentrations of four brain-specific biomarkers demonstrated significant differentiation between ICH patients and controls at all assessed time points (Days 1, 2, 3, 7, and 14; all p<0.05), with similar significant elevations observed for NfL, tau, and UCH-L1. Day 1 GFAP levels were markedly higher in ICH patients (median 9598 pg/mL compared with healthy controls (39.2 pg/mL; p<0.05). No significant differences were found between young and aged adult ICH subgroups. Neuroendocrine ACTH and AgRP levels were significantly higher in ICH patients compared to controls on both measured time points (Days 1 and 7). Conclusions The study’s findings suggest that GFAP, NfL, tau, UCH-L1, ACTH, and AgRP exhibit potential as biomarkers for differentiating spontaneous ICH patients from healthy controls. However, given the limitations of the current study design, these findings should be interpreted with caution and cannot be expected to translate directly into clinical practice. Further research is needed to assess these biomarkers’ roles in distinguishing stroke types and predicting ICH outcomes.

Exploratory profiling of serum small extracellular vesicle-associated miRNAs as candidate biomarkers for Moyamoya disease

Purpose Moyamoya disease (MMD) is a chronic progressive cerebrovascular disease with elevated rates of mortality and disability in children and adults. Therefore, early and accurate identification of MMD is crucial for good prognosis, effective therapeutics, and increased clinical survival rates. Serum small extracellular vesicles (EVs) have attracted significant attention as innovative liquid biopsy biomarkers for screening and diagnosing MMD. Patients and methods We performed small RNA (sRNA) sequencing to determine the miRNA profiles of serum-derived EVs and integrated the Weighted gene co-expression network analysis to identify the serum exosomal miRNA biomarkers within a screening cohort comprised of 10 adult MMD patients (38.7 ± 12.2 years), along with 10 age and gender-matched healthy controls (adult HCs, 41.0 ± 15.0 years) and 11 pediatric MMD patients (8.6 ± 2.2 years). Results Our results indicated that mRNA-derived fragments represented the largest annotated mapped fraction, whereas miRNAs were the principal small regulatory RNA class further analyzed for candidate biomarker discovery. Among them, specific EV-derived miRNAs, miR-378c, miR-205-5p and miR-374a-5p, were identified as closely related to disease progression in adult MMD patients. This miRNA exhibited significantly altered expression levels in adult MMD patients but not in pediatric cases, suggesting a potential role in the pathophysiology of MMD that might be associated with age-dependent factors or stages of disease development. The findings of this study emphasize the potential application of serum-EV-derived miRNAs as biomarkers for MMD, which could serve as an indicator for disease progression in adult patients. While the profiles of pediatric MMD were less significantly altered, the association of EV-derived miRNAs with adult disease progression presents a promising lead for adult-specific biomarkers. Conclusion These results provide a foundation for larger-scale studies with longitudinal follow-up to validate using serum exosomal miRNAs, particularly miR-205-5p and miR-374a-5p as non-invasive diagnostic and prognostic biomarkers for patients with adult MMD, enhancing clinical management and patient outcomes.

Serum Progranulin as an Early Diagnostic Biomarker in Acute Stroke

Aim Rapid differentiation between ischemic stroke (IS) and intracerebral hemorrhage (ICH) is crucial for early management. Progranulin, a multifunctional glycoprotein with neuroprotective and anti-inflammatory effects, is involved in neuronal survival and the control of inflammation. Although animal studies suggest a protective role, its diagnostic and prognostic value in acute human stroke remains uncertain. This study aimed to evaluate the diagnostic and prognostic significance of serum Progranulin in acute IS and ICH within six hours of onset. Materials and methods Forty-two acute stroke patients and forty-four healthy controls were enrolled. Inclusion criteria were an acute focal neurological deficit, presentation within six hours, and imaging confirmation of subtype. Exclusion criteria included prior stroke, trauma, tumors, systemic failure, or major comorbidities. Serum Progranulin was measured by ELISA. Statistical analyses included t-tests, Mann–Whitney U tests, ANOVA, chi-square tests, and ROC analyses. Results Serum Progranulin was significantly higher in stroke patients than in controls (69.6 ± 15.4 pg/mL vs 52.2 ± 18.9 pg/mL; p < 0.001). ROC analysis yielded a cut-off of 53 pg/mL (sensitivity 64%, specificity 84%; AUC 0.778, 95% CI 0.676–0.861). Progranulin did not differ between IS and ICH or by severity. No correlation existed with mortality, ICU admission, or hospital stay; only the Glasgow Coma Scale correlated with clinical outcomes. Conclusion Elevated levels of progranulin early in stroke support its potential as a diagnostic biomarker, but it does not distinguish stroke type or predict prognosis. Larger longitudinal studies are needed to clarify its clinical utility.

Plasma proteomic profiling characterizes candidate biomarkers of perimesencephalic non-aneurysmal subarachnoid hemorrhage.

OBJECT This study aims to explore the plasma proteomic profiles of angiographically confirmed pmSAH and aSAH, and to identify candidate protein biomarkers for discriminating these subtypes on a biological level. METHODS The differentially abundant proteins of plasma samples from patients with pmSAH (n = 30) and aSAH (n = 30) were analyzed by data-independent acquisition proteomics, and candidate biomarkers were screened. RESULTS 291 candidate biomarkers were obtained that could be used to distinguish pmSAH patients from aSAH patients, among which 76 were upregulated and 215 were downregulated in pmSAH. Subsequently, the 10 candidate biomarkers were validated by enzyme-linked immunosorbent assay in a validation cohort of 72 subjects. ORM1, ORM2, HP and NMNAT1 were specifically down-regulated in the pmSAH group, while ANP32A was specifically up-regulated in the pmSAH group. FGL2 was specifically up-regulated in the aSAH group. The combined model of ORM2, HP and ANP32A had the best discriminative power (AUC = 0.880). CONCLUSIONS This study identified ORM2, HP, and ANP32A as candidate biomarkers reflecting biological differences between pmSAH and aSAH. SIGNIFICANCE Although some proteomic studies have analyzed aneurysmal subarachnoid hemorrhage, to date, there have been no reports on the circulating proteomic analysis of pmSAH. Comparative analysis of the circulating proteomic differences between pmSAH and aSAH may not only help understand the causes of pmSAH, but also contribute to a deeper understanding of mechanisms showing how pmSAH differs from the formation and rupture mechanisms of intracranial aneurysms.

A proteomic signature for prognostic stratification in amyotrophic lateral sclerosis

Circulating protein profiling identifies prognostic biomarkers in amyotrophic lateral Sclerosis