Search

Background and Purpose: Clinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures., Methods: To evaluate total tau (t-tau), glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCHL1) and neurofilament light-chain (NfL) as fluid biomarkers in SCA3, ATXN3 mutation carriers (n = 143) and controls (n = 172) were clinically assessed, and the plasma concentrations of the four proteins were analysed on the Simoa HD-1 platform. Eleven ATXN3 mutation carrier cerebrospinal fluid samples were analysed for t-tau and phosphorylated tau (p-tau 181 ). A transgenic SCA3 mouse model (MJDTg) was used to measure cerebellar t-tau levels., Results: Plasma t-tau levels were higher in mutation carriers below the age of 50 compared to controls, and the Inventory of Non-Ataxia Signs was associated with t-tau in ataxic patients (p = 0.004). Pre-ataxic carriers showed higher cerebrospinal fluid t-tau and p-tau 181 concentrations compared to ataxic patients (p = 0.025 and p = 0.014, respectively). Cerebellar t-tau was elevated in MJDTg mice compared to wild-type (p = 0.033) only in the early stages of the disease. GFAP and UCHL1 did not show higher levels in mutation carriers compared to controls. Plasma NfL concentrations were higher in mutation carriers compared to controls, and differences were greater for younger carriers. The Scale for the Assessment and Rating of Ataxia was the strongest predictor of NfL in ataxic patients (p < 0.001)., Conclusion: Our results suggest that tau might be a marker of early disease stages in SCA3. NfL can discriminate mutation carriers from controls and is associated with different clinical variables. Longitudinal studies are required to confirm their potential role as biomarkers in clinical trials., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

To clarify the mechanism of brain impairment in Machado-Joseph disease (MJD), we measured the cerebrospinal fluid (CSF) levels of substance P in 7 patients (mean age 45.7 +/- 12.09 years) with this disease. Four patients had type I and three had type II disease. Findings were compared with those obtained in 14 age-matched controls, 8 patients with Parkinson's disease, 7 patients with multiple system atrophy, and 6 patients with myopathy. The CSF level of substance P was significantly (p = 0.0000) lower in the patients with MJD, being 44.5% of the control value. However, the mean CSF levels of substance P in the patients with Parkinson's disease, multiple system atrophy, or myopathy did not differ significantly from that in the control subjects. The alteration in the CSF level of substance P may be related to the neurological impairment observed in MJD.

We measured the cerebrospinal fluid (CSF) levels of beta-endorphin in 7 Japanese patients with Joseph disease and compared them with control values. The 7 patients included 4 with type I and 3 with type II disease; their mean age was 45.7 +/- 12.09 years. Diseased controls were matched in age to the patients studied. In these patients, CSF beta-endorphin level was significantly lower than in the controls (40% of normal values). An alteration in CSF beta-endorphin level may explain some of the neurological impairment found in Joseph disease.