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

Tobias Skillbäck,Joana Pereira,Henrik Zetterberg,Michelle M Mielke,Kaj Blennow,Silke Kern,Lars‐Olof Wahlund,Anna Zettergren,Sara Shams,Olof Lindberg,Ingmar Skoog,Lina Ryden,Eric Westman,Alejandra Machado

doi:10.1002/dad2.12141

Abstract

IntroductionAs 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.MethodsParticipants were derived from two Swedish samples: the population‐based H70 Study (n = 308, age 70) and a clinical routine cohort (CSF NfL, n = 8995, QAlb, n = 39252, age 0 to 95). In the population‐based study, QAlb and NfL were examined in relation to sex, cardiovascular risk factors, and cerebral white matter lesions (WMLs). In the clinical cohort, QAlb and NfL sex differences were tested in relation to age.ResultsMen had higher QAlb and NfL concentrations and had higher QAlb and NfL concentrations from adolescence throughout life. NfL was not related to WML, but QAlb correlated positively with WMLs.DiscussionThe 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

Introduction

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]

Objectives

Methods

Results

Conclusion