Neurofilaments in spinocerebellar ataxia type 3: blood biomarkers at the preataxic and ataxic stage in humans and mice.

EMBO Molecular Medicine
C. WilkeMatthis Synofzik

Abstract

With molecular treatments coming into reach for spinocerebellar ataxia type 3 (SCA3), easily accessible, cross-species validated biomarkers for human and preclinical trials are warranted, particularly for the preataxic disease stage. We assessed serum levels of neurofilament light (NfL) and phosphorylated neurofilament heavy (pNfH) in ataxic and preataxic subjects of two independent multicentric SCA3 cohorts and in a SCA3 knock-in mouse model. Ataxic SCA3 subjects showed increased levels of both NfL and pNfH. In preataxic subjects, NfL levels increased with proximity to the individual expected onset of ataxia, with significant NfL elevations already 7.5 years before onset. Cross-sectional NfL levels correlated with both disease severity and longitudinal disease progression. Blood NfL and pNfH increases in human SCA3 were each paralleled by similar changes in SCA3 knock-in mice, here also starting already at the presymptomatic stage, closely following ataxin-3 aggregation and preceding Purkinje cell loss in the brain. Blood neurofilaments, particularly NfL, might thus provide easily accessible, cross-species validated biomarkers in both ataxic and preataxic SCA3, associated with earliest neuropathological changes, and serve as p...Continue Reading

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Citations

Jan 14, 2021·Movement Disorders : Official Journal of the Movement Disorder Society·Camila Maria de OliveiraLaura Bannach Jardim
Mar 19, 2021·Acta Neurologica Scandinavica·Christian Barro, Henrik Zetterberg
Apr 6, 2021·Annals of Clinical and Translational Neurology·Christoph KesslerRebecca Schüle
Apr 10, 2021·Journal of the Neurological Sciences·Meng-Ling ChenSheng-Han Kuo
May 22, 2021·Annals of Clinical and Translational Neurology·Sarah M BrookerPuneet Opal
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Jan 27, 2022·Expert Review of Neurotherapeutics·Shaila D GhanekarTheresa A Zesiewicz

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Methods Mentioned

BETA
antisense oligonucleotides
biopsies

Clinical Trials Mentioned

NCT01037777

Software Mentioned

Catwalk
ODYSSEY Server
Simoa
ImageJ
Catwalk X
AxioVision
Quanterix

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