Abstract Introduction As cerebrospinal fluid (CSF) neurofilament light protein (NfL) and the CSF/serum albumin ratio (Q Alb ) are used in the clinical routine, the impact of demographic factors on these biomarkers is important to understand. Methods Participants were derived from two Swedish samples: the population‐based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, Q Alb , n = 39252, age 0 to 95). In the population‐based study, Q Alb and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, Q Alb and NfL sex differences were tested in relation to age. Results Men had higher Q Alb and NfL concentrations and had higher Q Alb and NfL concentrations from adolescence throughout life. NfL was not related to WML, but Q Alb correlated positively with WMLs. Discussion The CSF NfL sex difference could not be explained by vascular pathology. Future studies should consider using different reference limits for men and women.
Sex differences in CSF biomarkers for neurodegeneration and blood‐brain barrier integrity
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.