Sex differences in CSF biomarkers for neurodegeneration and blood‐brain barrier integrity

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.