Sex differences in levels of plasma neurofilament light and total tau in adults with Down syndrome

Abstract

AbstractBackgroundPlasma neurofilament light (NfL) and total tau (t‐tau) are emerging as promising biomarkers of Alzheimer’s disease (AD) in adults with Down Syndrome (DS). Sex may influence the levels of these biomarkers however, research on sex differences in these biomarkers is limited. In this study, we examined whether sex influences plasma levels and clinical classification accuracy of NfL and t‐tau.MethodWe performed a cross‐sectional analysis of 275 adults with DS (106 males; 169 females) from a community‐based cohort. Levels of plasma NfL and t‐tau were measured using the Simoa platform. Based on consensus diagnosis using a battery of direct neuropsychological testing and informant interviews, participants were classified into three clinical dementia groups: cognitively stable (CS), mild‐cognitive impairment (MCI‐DS) and Alzheimer’s dementia (AD‐DS). Two‐way analysis of covariance was used to assess group differences in males and females, adjusting for age. Post‐hoc pairwise comparisons were adjusted for multiple comparisons using the Bonferroni correction. Receiver operating characteristic analyses were conducted to evaluate the performance of the biomarkers to classify dementia status in males and females, separately.ResultIn this study, 27 (16%) and 10 (6%) females while 12 (11%) and 13 (12%) males exhibited MCI‐DS and AD‐DS, respectively. Females were, on average, 4.5 years younger than males. Age‐adjusted levels of plasma t‐tau (pinteraction = 0.047), but not NfL (pinteraction = 0.138), significantly differed by sex. NfL levels were higher in MCI‐DS and AD‐DS groups than in the CS group in both sexes (all padjusted < 0.05). T‐tau levels were significantly higher in the MCI‐DS and AD‐DS (both padjusted < 0.01) groups than in the CS group in females but did not differ across clinical groups in males. NfL showed excellent accuracy in females (range AUCNfL: 0.74‐0.97) and males (AUCNfL: 0.71‐0.88), while t‐tau showed classification utility in females (AUCt‐tau:0.69‐0.90), but not in males (AUCt‐tau: 0.48‐0.66).ConclusionOur findings suggest that levels and accuracy of plasma NfL and t‐tau to classify dementia differed by sex in adults with DS. These differences underscore the need to further elucidate sex specific patterns of fluid biomarkers, critical in the development of personalized medicine approaches in AD.