Serum neurofilament light levels in normal aging and their association with morphologic brain changes

Neurofilament light (NfL) protein is a marker of neuro-axonal damage and can be measured not only in cerebrospinal fluid but also in serum, which allows for repeated assessments. There is still limited knowledge regarding the association of serum NfL (sNfL) with age and subclinical morphologic brain changes and their dynamics in the normal population. We measured sNfL by a single molecule array (Simoa) assay in 335 individuals participating in a population-based cohort study and after a mean follow-up time of 5.9 years (n = 103). Detailed clinical examination, cognitive testing and 3T brain MRI were performed to assess subclinical brain damage. We show that rising and more variable sNfL in individuals >60 years indicate an acceleration of neuronal injury at higher age, which may be driven by subclinical comorbid pathologies. This is supported by a close association of sNfL with brain volume changes in a cross-sectional and especially longitudinal manner.


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Our investigation was based on data and material from the prospective and ongoing Austrian Stroke Prevention Family Study (ASPS-Fam), which is an extension of the Data exclusions Thirty-six subjects had to be excluded due to one or more of following exclusion criteria: diagnosis or suspicion of dementia (MMSE<=24 or problems (failure of one task in the Mini-Cog test) of memory: n=11), visible brain infarcts on MRI (n=19), a history of stroke (n=9), other diseases (chronic myeloid leukemia) (n=1). This left a total of 335 participants to investigate sNfL in an aging population. From all subjects, 103 agreed on a follow-up scan and the mean follow-up time was 5.59 years (±0.97, min=3.99, max=6.94). A total of 8 follow-up cases were excluded for new onset stroke (n=3), heart disease (n=2), transient ischemic attack (n=1), brain hemorrhage (n=1) and orofacial dyskinesia (n=1) between baseline and follow-up assessment.

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