ArticleAnnals of clinical and translational neurology2026
Prognostic Value of Neurofilament Light Chain and Glial Fibrillary Acidic Protein in ALD-Related Myelopathy.
Article in Annals of clinical and translational neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
backgroundX-linked adrenoleukodystrophy (X-ALD) is a neurometabolic disorder caused by pathogenic variants in ABCD1, leading to slowly progressive spinal cord disease in nearly all affected men. Sensitive biomarkers to quantify disease severity and predict progression are needed for clinical care and trial design. Plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) are promising biomarkers reflecting axonal and astroglial injury. This study evaluated their prognostic value for spinal cord disease progression in X-ALD.
methodsIn a prospective, seven-year longitudinal study, 66 adult male X-ALD patients without cerebral involvement were followed. Plasma NfL and GFAP were measured using single-molecule array (Simoa) technology. Patients were stratified by baseline biomarker levels using cohort-based fourth-quartile cut-offs (NfL < 15.7 vs. ≥ 15.7 pg/mL; GFAP < 78.7 vs. ≥ 78.7 pg/mL). Age-adjusted NfL residuals were calculated from baseline log-transformed NfL regressed on age. Longitudinal trajectories of the EDSS, SSPROM, and 6-MWT were analyzed using linear mixed-effect models.
resultsHigh baseline NfL was associated with faster EDSS progression (p < 0.001) and steeper SSPROM decline, with differences emerging within the first year. Overall plasma NfL levels remained stable over time (p = 0.111). Age-adjusted NfL residuals showed significant slope differences between the mean and high (+1 SD) and very high (+2 SD) groups. GFAP stratification showed limited prognostic value, with only a significant decline in both groups for SSPROM.
interpretationBaseline plasma NfL is a robust prognostic biomarker for spinal cord disease progression in adult X-ALD and supports its use for patient stratification in clinical trials, whereas GFAP shows limited standalone utility.
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