A 14-year longitudinal study of neurofilament light chain dynamics in premanifest and transitional Huntington’s disease
Background Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington’s disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct...
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| Published in: | Journal of neurology Vol. 271; no. 12; pp. 7572 - 7582 |
|---|---|
| Main Authors: | , , , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
Berlin/Heidelberg
Springer Berlin Heidelberg
01-12-2024
Springer Nature B.V |
| Subjects: | |
| Online Access: | Get full text |
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| Summary: | Background
Growing evidence supports the value of neurofilament light (NfL) as a prognostic biomarker in premanifest Huntington’s disease (HD). To date, however, there has been no longitudinal study exceeding 3 years examining either its serial dynamics or predictive power in HD. We aimed to conduct the first such study.
Methods
Serum NfL was sampled using ultrasensitive immunoassay at four timepoints across a 14-year period in a cohort of HD gene carriers (
n
= 21) and controls (
n
= 14). Gene carriers were premanifest at baseline. Clinical features of HD were evaluated by Unified Huntington’s Disease Rating Scale (UHDRS TMS), Montreal Cognitive Assessment (MoCA), Trail A/B task, Symbol Digit Modalities Task and semantic/phonemic fluency tasks.
Results
14/21 HD gene carriers converted to prodromal or manifest disease by the final timepoint (“converters”). At baseline and each subsequent timepoint, NfL levels were higher in converters than in non-converters and controls (
p
= < 0.001–0.03,
η
p
2
= 0.25–0.66). The estimated rate of change in NfL was higher in converters than in non-converters (
p
= 0.03) and controls (
p
= 0.001). Baseline NfL was able to discriminate converters from non-converters (area under curve = 1.000,
p
= 0.003). A higher rate of change in NfL was predictive of more severe motor (UHDRS-TMS
p
= 0.007,
β
= 0.711,
R
2
= 0.468) and cognitive deficits (MoCA
p
= 0.007,
β
= − 0.798,
R
2
= 0.604; Trail B,
p
= 0.007,
β
= 0.772,
R
2
= 0.567; phonemic fluency
p
= 0.035,
β
= − 0.632,
R
2
= 0.345).
Conclusions
Our data suggest that (1) NfL longitudinal dynamics in premanifest/transitional HD are non-constant; rising faster in those closer to disease onset, and (2) NfL can identify individuals at risk of conversion to manifest disease and predict clinical trajectory, > 10 years from disease onset. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0340-5354 1432-1459 1432-1459 |
| DOI: | 10.1007/s00415-024-12700-x |