Abstract
Objective: Serum neurofilament light (sNfL) is a promising marker for neuro-axonal damage and it is now well known that its levels also increase with higher age. However, the effect of other determinants besides age is still poorly investigated. We therefore aimed to identify factors influencing the sNfL concentration by analysing a large set of demographical, life-style and clinical variables in a normal aging cohort.Methods: sNfL was quantified by single molecule array (Simoa) assay in 327 neurologically inconspicuous individuals (median age 67.8±10.7 years, 192 female) who participated in the Austrian Stroke Prevention Family Study (ASPS-Fam). Random forest regression analysis was used to rank the association of included variables with sNfL in the entire cohort and in age-stratified subgroups. Linear regression then served to identify factors independently influencing sNfL concentration.Results: Age (β=0.513, p<0.001) was by far the most important factor influencing sNfL, which was mainly driven by individuals ≥60 years. In age stratified sub-groups, body mass index (BMI) (β=-0.298, p<0.001) independently predicted sNfL in individuals aged 38-60 years. In individuals ≥60 years, age (β=0.394, p<0.001), renal function (β=0.376, p<0.001), blood volume (β=-0.198, p=0.008) and high density lipoprotein (HDL) (β=0.149, p=0.013) were associated with sNfL levels.Conclusions: Age is the most important factor influencing sNfL concentrations, getting increasingly relevant in elderly people. BMI further influences sNfL levels, especially at younger age, whereas renal function gets increasingly relevant in the elderly.
Highlights
In the last years, the neurofilament light (NfL) chain protein has evolved into the most promising biomarker to indicate neuro-axonal damage being at the doorstep of clinical application
When considering the entire cohort we found significant correlations of Serum neurofilament light (sNfL) with age, renal function (estimated glomerular filtration rate, creatinine and urea), liver function (glutamate pyruvate transaminase (GPT)), cerebrovascular risk factors (systolic blood pressure, high density lipoprotein (HDL) and Hba1c) and blood volume
Overall body mass index (BMI) was unrelated to sNfL in the total cohort, we found more indication of a correlation between sNfL and BMI in younger individuals (
Summary
The neurofilament light (NfL) chain protein has evolved into the most promising biomarker to indicate neuro-axonal damage being at the doorstep of clinical application. With the advent of a single-molecule array (SiMoA) technology, reliable quantification of low NfL concentrations in the peripheral blood compared to cerebrospinal fluid (CSF) became available [3] This cutting-edge technique facilitated to comprehensively study this protein as diagnostic and prognostic marker in various acute and chronic neurological disorders [1]. It is well known that NfL increases in normal aging, which is paralleled by a higher variability in the elderly [4, 5], making it difficult to correctly interpret this marker on an individual level It is further not completely clear if other factors besides age may impact NfL levels, and if this may vary across different age ranges. We hypothesized that factors which confound sNfL as well as their relative impact on this marker may change during the course of aging
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