Tau and neurofilament light-chain as fluid biomarkers in spinocerebellar ataxia type 3.
biomarkers
cerebellum
neurofilaments
spinocerebellar ataxias
tau
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
Aug 2022
Aug 2022
Historique:
revised:
06
04
2022
received:
22
02
2022
accepted:
24
04
2022
pubmed:
29
4
2022
medline:
19
7
2022
entrez:
28
4
2022
Statut:
ppublish
Résumé
Clinical trials in spinocerebellar ataxia type 3 (SCA3) will require biomarkers for use as outcome measures. 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 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 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.
Sections du résumé
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
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
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.
Identifiants
pubmed: 35478426
doi: 10.1111/ene.15373
pmc: PMC9543545
mid: NIHMS1838989
doi:
Substances chimiques
Biomarkers
0
Mapt protein, mouse
0
Neurofilament Proteins
0
neurofilament protein L
0
tau Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
2439-2452Subventions
Organisme : NINDS NIH HHS
ID : R01 NS088689
Pays : United States
Organisme : European Research Council
ID : 681712
Pays : International
Organisme : NINDS NIH HHS
ID : P01 NS084974
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097273
Pays : United States
Organisme : Medical Research Council
ID : MR/N028767/1
Pays : United Kingdom
Organisme : NINDS NIH HHS
ID : R21 NS084528
Pays : United States
Informations de copyright
© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
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