| Title: | Plasma neurofilament light levels show elevation two years prior to diagnosis of amyotrophic lateral sclerosis in the UK Biobank |
| Journal: | Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration |
| Published: | 27 Nov 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38013452/ |
| DOI: | https://doi.org/10.1080/21678421.2023.2285428 |
| Citations: | 4 (4 in last 2 years) as of 8 Aug 2024 |
Publication 8254
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Abstract
OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a debilitating neurodegenerative disease with profound unmet need. In patients carrying genetic mutations, elevations in neurofilament light (NfL) have been shown to precede symptom onset, however, the natural history of NfL in general ALS patients is less characterized.</p>
METHODS: We performed a secondary analysis of the UK Biobank Pharma Proteomics Project (UKB-PPP), a subset of the UK Biobank, a population-based cohort study in the United Kingdom, to examine plasma NfL levels in 237 participants subsequently diagnosed with ALS. We applied logistic and Cox proportional hazards regression to compare cases to 42,752 population-based and 948 age and sex-matched controls. Genetic information was obtained from exome and genotype array data.Results and Conclusions: We observed that NfL was 1.42-fold higher in cases vs population-based controls. At two to three years pre-diagnosis, NfL levels in patients exceeded the 95th percentile of age and sex-matched controls. A time-to-diagnosis analysis showed that a 2-fold increase in NfL levels was associated with a 3.4-fold risk of diagnosis per year, with NfL being most predictive of case status at two years (AUC = 0.96). Participants with genetic variation that might put them at risk for familial disease (N = 46) did not show a different pattern of association than those without (N = 191).</p>
DISCUSSION: Our findings show that NfL is elevated and discriminative of future ALS diagnosis up to two years prior to diagnosis in patients with and without genetic risk variants.</p>
7 Authors
- Erin N. Smith
- Jonghun Lee
- Daria Prilutsky
- Stephen Zicha
- Zemin Wang
- Steve Han
- Neta Zach
2 Applications
| Application ID | Title |
|---|---|
| 26041 | Large-Scale Sequencing in the UK Biobank to Facilitate Gene Discovery, Genome Sciences, and Precision Medicine |
| 65851 | Large-scale proteomic profiling to facilitate genetics-guided drug discovery and precision medicine: The UK Biobank - Pharma Proteomics Project (UKB-PPP) |
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