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The following is a summary of “Elevated serum concentrations of GFAP in hereditary transthyretin amyloidosis since pre-symptomatic stages,” published in the April 2025 issue of Journal of Neurology by Plantone et al. 

Hereditary transthyretin amyloidosis (ATTRv) is a rare genetic disorder linked to TTR gene mutations. Glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) are potential biomarkers of astrocyte activation and neuroaxonal injury. 

Researchers conducted a retrospective study to assess serum GFAP (sGFAP) and NfL (sNfL) levels in patients with ATTRv, pre-symptomatic subjects, and healthy controls (HCs) as biomarkers for disease progression and central nervous system (CNS) involvement. 

They conducted a multicenter cross-sectional study with 111 patients with ATTRv (56 symptomatic, 55 pre-symptomatic) and 183 HCs. Serum levels of sGFAP and sNfL were measured using ultrasensitive immunoassays. Statistical comparisons were made using ANCOVA models (age and sex adjusted), and correlations were examined between serum biomarkers and disease severity (Neuropathy Impairment Score, NIS). 

The results showed elevated sGFAP levels in symptomatic (median: 238.35 pg/ml) and pre-symptomatic subjects (median: 105.50 pg/ml) vs. HCs (median: 75.5 pg/ml, P < 0.001). sNfL was elevated only in symptomatic patients (median: 43.68 pg/ml) compared to pre-symptomatic subjects (median: 9.36 pg/ml) and HCs (median: 7.54 pg/ml, P < 0.001). Both biomarkers correlated significantly with NIS. Female HCs had higher sGFAP levels than males (median: 88.6 pg/ml vs. 59.8 pg/ml; P 0.011). 

Investigators found that sGFAP and sNfL mark distinct ATTRv stages, with sGFAP indicating early preclinical changes and sNfL correlating with neurological progression. They also observed sex differences in sGFAP levels among HCs, suggesting sex should be considered as a covariate in biomarker analyses. 

Source: link.springer.com/article/10.1007/s00415-025-13072-6