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Tau and neurofilament light-chain as fluid biomarkers in spinocerebellar ataxia type 3

Abstract: 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-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). Pre-ataxic carriers showed higher cerebrospinal fluid 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 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.

Otras publicaciones de la misma revista o congreso con autores/as de la Universidad de Cantabria

 Fuente: Eur J Neurol . 2022 Aug;29(8):2439-2452

Editorial: Wiley

 Año de publicación: 2022

Nº de páginas: 16

Tipo de publicación: Artículo de Revista

 DOI: 10.1111/ene.15373

ISSN: 1351-5101,1468-1331

Url de la publicación: https://www.doi.org/10.1111/ene.15373

Autoría

GARCIA-MORENO, HECTOR

PRUDENCIO, MERCEDES

THOMAS-BLACK, GILBERT

SOLANKY, NITA

JANSEN-WEST, KAREN R

HANNA AL-SHAIKH, RANA

HESLEGRAVE, AMANDA

ZETTERBERG, HENRIK

SANTANA, MAGDA M

PEREIRA DE ALMEIDA, LUIS

VASCONCELOS-FERREIRA, ANA

JANUÁRIO, CRISTINA

FABER, JENNIFER

KLOCKGETHER, THOMAS

REETZ, KATHRIN

RAPOSO, MAFALDA

FERREIRA, ANA F

LIMA, MANUELA

SCHÖLS, LUDGER