Serum glial fibrillary acidic protein is elevated in early-stage late-onset essential tremor and associated with tremor progression.

The role of neurodegeneration in essential tremor (ET) remains debated, particularly in patients with late disease onset. Neuropathological studies have identified structural changes in the Purkinje cells and its connections. Recent studies additionally suggested a role of cerebellar astrocytes. Increased levels of serum glial fibrillary acidic protein (sGFAP), an astrocytic intermediate filament, were found in various neuroinflammatory and neurodegenerative diseases. The objective of this case-control study was to investigate the role of sGFAP in ET focusing on early-stage late-onset patients. sGFAP was quantified by single molecule array at baseline and follow-up in 36 ET-patients (median follow-up period 5.3 years) and 36 age-matched healthy controls (4.9 years). ET-patients were assessed both at baseline and follow-up using the Fahn-Tolosa-Marin-Tremor-Rating-Scale. The ET group was stratified (1) by median age at onset and median disease duration in early-stage late-onset and early-onset/late-stage ET, and (2) by median sGFAP-level at baseline. Early-stage late-onset ET-patients had higher baseline-sGFAP than controls (p = 0.023) and higher follow-up-sGFAP and annual sGFAP-increase than both controls (p = 0.023; p = 0.007) and early-onset/late-stage ET-patients (p = 0.021; p = 0.024). Baseline sGFAP-level correlated with tremor severity at follow-up in the early-stage late-onset (r