Elevated serum neurofilament light chain protein in patients with essential tremor

Abstract

Background and purposeQuantification of neurofilament light chain protein in serum (sNfL) enables the neuro‐axonal damage in peripheral blood to be reliably assessed and monitored. There is a long‐standing debate whether essential tremor represents a ‘benign’ tremor syndrome or whether it is linked to neurodegeneration. This study aims to investigate sNfL concentrations in essential tremor compared to healthy controls (cross‐sectionally and longitudinally) and to assess whether sNfL is associated with motor and nonmotor markers of disease progression.MethodsData of patients with essential tremor from our prospective registry on movement disorders (PROMOVE) were retrospectively analysed. Age‐, sex‐ and body‐mass‐index‐matched healthy controls were recruited from an ongoing community‐dwelling aging cohort. sNfL was quantified by an ultra‐sensitive single molecule array (Simoa). All participants underwent detailed clinical examination at baseline and after approximately 5 years of follow‐up.ResultsThirty‐seven patients with clinically diagnosed essential tremor were included and 37 controls. The essential tremor group showed significantly higher sNfL levels compared to healthy controls at baseline and follow‐up. sNfL levels increased over time in both groups, and the slope of sNfL increase was similar in the essential tremor and healthy control groups. Comparing patients with a disease duration under 5 years to those with a longer disease duration, the former group had a significantly greater increase of sNfL over time, which strongly correlated to worsening of tremor and cognition.ConclusionOur findings indicate that neurodegeneration, possibly happening at an early disease stage, might play a role in the pathophysiology of essential tremor.

Proteomic profile analysis of plasma and aqueous humor from glaucoma and non-glaucomatous patients

“…NEFL is a well-established marker of neurodegeneration 42,[44][45][46][47]86 and similar to our finding, has previously been reported to be elevated in glaucomatous AH in humans and animal models 41, 43, 87 . In fact, NEFL had the highest correlation with IOP in all donors in this study, providing additional confidence that NEFL in the AH may indeed be a suitable biomarker for glaucomatous neurodegeneration and ocular hypertension.…”

“…The copyright holder for this preprint (which this version posted April 15, 2024. ; https://doi.org/10.1101/2024.04.11.588885 doi: bioRxiv preprint measurements (R 2 = 0.3067). Since NEFL is a widely accepted marker for several neurodegenerative diseases including glaucoma [41][42][43][44][45][46][47][48][49][50] , we then decided to further investigate if levels of NEFL correlated with other SOMAmers identified in glaucomatous donors. We calculated the Pearson's correlation coefficient of NEFL and rest of the proteins and identified 29 proteins that are positively or negatively correlated with NEFL (|r > 0.4|), including TEAD3, CNTF, C4A, C4B and CCL27 (Figure 5).…”