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Prediagnostic Neurofilament Light Chain Levels in Amyotrophic Lateral Sclerosis
Kjetil Bjornevik1, Eilis J O'Reilly2, Samantha Molsberry2
1From the Departments of Nutrition (K.B., E.J.O., S.M., A.A.) and Epidemiology (A.A.), Harvard T.H. Chan School of Public Health, Boston, MA; School of Public Health, College of Medicine (E.J.O.), University College Cork, Ireland; Epidemiology Program (L.N.K., L.L.M.), University of Hawaii Cancer Center, Honolulu; Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Healey Center for ALS (S.P.), and Department of Neurology (M.A.S.), Massachusetts General Hospital, Boston; Harvard Medical School (S.P., M.A.S.), Boston, MA; Clinical Trial Unit, Department of Clinical Research (P.B.), and Neurologic Clinic and Policlinic, MS Center and Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Biomedicine and Clinical Research (J.K.), University Hospital Basel, University of Basel, Switzerland; and Channing Division of Network Medicine (A.A.), Brigham and Women's Hospital and Harvard Medical School, Boston, MA. kbjorne@hsph.harvard.edu.
Plasma neurofilament light chain (NfL) levels are elevated before amyotrophic lateral sclerosis (ALS) diagnosis. These findings suggest NfL is a potential early biomarker for ALS.
Area of Science:
- Neurology
- Biomarkers
- Neurodegenerative Diseases
Background:
- Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease.
- Early detection of ALS is crucial for timely intervention and management.
- Identifying reliable prediagnostic biomarkers for ALS remains a significant challenge.
Purpose of the Study:
- To determine if plasma neurofilament light chain (NfL) levels are elevated in individuals prior to an ALS diagnosis.
- To investigate the association between prediagnostic NfL levels and metabolic alterations in ALS patients.
Main Methods:
- A matched case-control study was conducted using data from three large prospective US cohorts.
- 84 individuals who developed ALS and had prediagnostic plasma samples were identified.
- Plasma NfL levels were measured and analyzed using conditional logistic regression, adjusting for relevant covariates.
Main Results:
- Elevated plasma NfL levels were significantly associated with an increased risk of ALS when samples were collected within 5 years of diagnosis.
- No significant association was found for samples collected further from the diagnosis date.
- While 21 metabolites correlated with prediagnostic NfL in ALS cases, none remained significant after multiple comparison adjustments.
Conclusions:
- Plasma NfL levels are elevated in the prediagnostic stages of ALS.
- NfL shows potential as a valuable biomarker for detecting ALS in its earliest phases.
- Further research is warranted to explore the role of NfL and its relationship with metabolic changes in ALS pathogenesis.
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