AxD is a rare heritable astrocytopathy characterized by accumulation of mutant glial fibrillary acidic protein in white matter, striatal and brainstem structures. Medullary involvement, and particularly the development of medullary mass-like lesions, is hypothesized to mediate the intractable emesis distinctive of this leukodystrophy. GDF15 is an inflammatory cytokine involved in emesis and cachexia via binding to its receptor in the medulla. This mechanism suggests a possible pathophysiologic role of GDF15 in centrally-mediated emesis in AxD.

Plasma GDF15 levels were assessed in AxD patients (n=67) and age-matched leukodystrophy controls (n=47). Cerebrospinal fluid (CSF) GDF15 levels were evaluated in AxD patients (n=44) and age-matched controls (n=27) enrolled in an institutional biorepository. Longitudinal samples were available in a subset of AxD patients. Generalized estimating equations compared GDF15 levels between AxD and controls, and further evaluated the relationship between emesis, medullary mass-like lesions and GDF15 levels in AxD patients, controlling for age. Spearman correlation assessed relationship between plasma and CSF GDF15 levels.

GDF15 levels are elevated more than 10-fold in CSF of AxD patients compared to controls, and do not correlate with plasma levels. CSF GDF15 levels are inversely correlated with age, possibly reflecting differences in disease activity by age.