Abstract
AbstractBackgroundCSF neurofilament light protein (NfL) is an important biomarker in several neurologic diseases. CSF NfL concentrations are known to increase with age, but sex differences have been less examined. The CSF/serum albumin ratio (QAlb) is a biomarker for blood‐brain barrier integrity, which has previously been found to be higher in men. As NfL and QAlb are used in clinical routine, the impact of demographic factors on these biomarkers is important to understand.MethodParticipants were derived from two samples. The first was a population‐based cohort of 308 70‐year olds from the Gothenburg H70 Birth Cohort Study, Sweden. The second data set comprised CSF NfL and QAlb results from 8995 and 39252 subjects respectively, generated in clinical practice between 2005‐2012 in Gothenburg, Sweden. In the population‐based study, QAlb and NfL concentrations were examined in relation to sex, cardiovascular risk factors, and MRI signs of cerebral white matter lesions. In the clinical routine cohort, sex differences in QAlb and NfL were tested in relation to age.ResultIn the population‐based sample, men had higher QAlb and NfL concentrations than women. NfL was not related to cerebral vascular pathology, but QAlb correlated positively with several measures of white matter lesions. In the clinical routine cohort, men also had higher QAlb and NfL concentrations from adolescence and throughout life.ConclusionQAlb ratios and CSF NfL levels are higher in men throughout life. The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
Highlights
As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the Cerebrospinal fluid (CSF)/serum albumin ratio (QAlb) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand
Interpretation: Our findings show that CSF NfL and QAlb are higher in men from adolescence throughout life and in CSF NFL irrespective of white matter pathology
In this study we aimed to identify and examine sex differences in CSF NfL, a non-specific biomarker for neurodegeneration, and QAlb, a biomarker for BBB integrity, among non-demented 70-year-olds derived from a population-based sample and a clinical routine cohort, spanning ages 0 to 95
Summary
As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (QAlb) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand. Cerebrospinal fluid (CSF) neurofilament light protein (NfL) and CSF/serum albumin ratio (QAlb) are widely used biomarkers that aid diagnostics and disease monitoring of neurodegenerative and neuroinflammatory diseases in both research and clinical settings. It is known that CSF NfL increases with age, but it has been less examined if there are sex differences or other factors such as cardiovascular pathology that alter concentrations and reference ranges. A recent meta-analysis found higher NfL concentrations in men among healthy controls and some neurodegenerative conditions, and the same finding was observed in a small data set from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) study.[9,10] the relation with possible vascular factors was not examined. Reference ranges for QAlb and CSF NfL are commonly adjusted by age, but no adjustment due to sex is applied.[12,13]
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