Garcia-Moreno, Hector;
Prudencio, Mercedes;
Thomas-Black, Gilbert;
Solanky, Nita;
Jansen-West, Karen R;
Hanna Al-Shaikh, Rana;
Heslegrave, Amanda;
... Giunti, Paola; + view all
(2022)
Tau and neurofilament light-chain as fluid biomarkers in spinocerebellar ataxia type 3.
European Journal of Neurology
, 29
(8)
pp. 2439-2452.
10.1111/ene.15373.
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Euro J of Neurology - 2022 - Garcia‐Moreno - Tau and neurofilament light‐chain as fluid biomarkers in spinocerebellar.pdf Download (1MB) | Preview |
Abstract
BACKGROUND: Clinical trials in 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 plasma concentrations of the four proteins were analysed on the Simoa HD-1 platform. Eleven ATXN3 mutation carrier CSF samples were analysed for t-tau and phosphorylated tau (p-tau181 ). 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). Preataxic carriers showed higher CSF t-tau and p-tau181 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 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 to different clinical variables. Longitudinal studies are required to confirm their potential role as biomarkers in clinical trials.
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