Extensive evidence supports the claim that serum neuro lament 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, re ected as N-acetyl aspartate/creatine (NAA/Cr). These associations remained signi cant after multiple comparison corrections. Our results con rmed 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.

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.

Spinocerebellar ataxia type 3 (SCA3), as the most frequent autosomal dominant ataxia worldwide, is characterized by progressive cerebellar ataxia, dysarthria and extrapyramidal signs. Additionally, autonomic dysfunction, as a common clinical symptom, present in the later stage of SCA3. Here, we report a 44-year-old male patient with early feature of autonomic dysfunction includes hyperhidrosis and sexual dysfunction, followed by mild ataxia symptoms. The Unified Multiple System Atrophy Rating Scale (UMSARS) indicated significant dysautonomia during autonomic function testing. Combination of early and autonomic abnormalities and ataxia would be more characteristic of the cerebellar type of multiple system atrophy (MSA-C), the patient's positive family history and identification of an ATXN3 gene mutation supported SCA3 diagnosis. To best of our knowledge, the feature as the initial presentation in SCA3 has not been described. Our study demonstrated that autonomic dysfunction may have occurred during the early stages of SCA3 disease.