Abstract
Increased neurofilament light (NfL; NEFL) protein in biofluids is reflective of neurodegeneration and has gained interest as a biomarker across neurodegenerative diseases. In spinocerebellar ataxia type 3 (SCA3), the most common dominantly inherited ataxia, patients exhibit progressive NfL increases in peripheral blood when becoming symptomatic, and NfL remains stably elevated throughout further disease course. However, progressive NfL changes are not yet validated in relevant preclinical SCA3 animal models, hindering its application as a biomarker during therapeutic development. We used ultra-sensitive single-molecule array (Simoa) to measure blood NfL over disease progression in YACQ84 mice, a model of SCA3, assessing relationships with measures of disease severity including age, CAG repeat size and magnetic resonance spectroscopy. YACQ84 mice exhibited plasma NfL increases that were concomitant with ataxia-related motor deficits as well as increased serum NfL, which correlated with previously established neurometabolite abnormalities, two relevant measures of disease in patients with SCA3. Our findings establish the progression of NfL increases in the preclinical YACQ84 mouse, further supporting the utility of blood NfL as a peripheral neurodegeneration biomarker and informing on coinciding timelines of different measures of SCA3 pathogenesis.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
