Extensive evidence supports the claim that serum neurofilament light chain (sNfL) can be used as a biomarker for monitoring disease severity in patients with spinocerebellar ataxia type 3 (SCA3). However, little is known about the associations between sNfL levels and neurochemical alterations in SCA3 patients. Serum samples were collected from ATXN3 mutation carriers (n = 20) and normal controls (n = 14). sNfL levels, measured by a single-molecule array, were compared between SCA3 patients and controls. We explored the relationship between sNfL levels and metabolic changes via magnetic resonance spectroscopy (MRS) scans. sNfL levels in SCA3 patients were higher than those in healthy controls, and these levels were correlated with disease severity. Associations emerged between the elevation of sNfL levels and lower brain metabolite changes, reflected as N-acetyl aspartate/creatine (NAA/Cr). These associations remained significant after multiple comparison corrections. Our results confirmed that serum sNfL levels are increased in SCA3 and are correlated with cerebellar hemisphere metabolic changes. Brain metabolic changes and sNfL levels show promise as potential complementary biomarkers for clinical trials for patients with SCA3.
