Introduction: Distinguishing the etiology of intracerebral hemorrhage (ICH), whether due to hypertension or cerebral amyloid angiopathy (CAA), remains a critical clinical challenge, particularly as imaging often reveals overlapping pathologies in older adults. Inflammation is central to ICH pathophysiology and may provide diagnostic insights. We evaluated a panel of neuroinflammatory biomarkers to explore whether distinct profiles could help differentiate hypertensive ICH from CAA-related hemorrhage. Hypothesis: We hypothesized that circulating neuroinflammatory biomarkers could help distinguish hypertensive ICH from CAA. Methods: Fifty-six patients with acute ICH (mean age 74 ± 7.9) were enrolled: 28 with hypertensive ICH and 28 with CAA-related hemorrhage. Serum samples were obtained within 72 hours of onset. Twenty-four age- and sex-matched healthy controls (mean age 75 ± 12.8) without neurologic disease provided single time-point samples. Exclusion criteria included active cancer, recent blood transfusion, or active substance abuse. Biomarker levels (BLC/CXCL13, TREM2, IL-34, MIF, RAGE, YKL-40, ThermoFisher) were quantified using a multiplex immunoassay. Results: Compared with controls, patients with CAA demonstrated significantly elevated BLC (CXCL13) (p = 0.037) and TREM2 (p = 0.038). No significant differences were observed in IL-34, MIF, RAGE, or YKL-40. Biomarker patterns between hypertensive ICH and CAA did not differ significantly in this pilot cohort, although a trend was seen towards higher levels of YKL-40 in CAA patients. Conclusion: This pilot study suggests that selected neuroinflammatory biomarkers, particularly CXCL13 and TREM2, are elevated in CAA-related ICH compared with healthy aging controls. While these findings do not clearly distinguish CAA from hypertensive ICH, they highlight the potential of inflammatory profiling to enhance phenotyping of hemorrhagic stroke and guide future biomarker discovery. Further studies in larger cohorts are warranted to refine diagnostic signatures in ICH.
John et al. (Thu,) studied this question.