Increased p-Tau181 Levels After Overnight Wakefulness Are Associated With Neuroticism in Young Women

Night shift work can impair attention and increase biomarkers linked to neurodegenerative processes. Understanding factors that influence resilience to, or vulnerability under, sleep loss is therefore essential for identifying groups at particular risk. In this within-subjects study, we examined two potential modulators of vulnerability in 54 healthy, naturally cycling women aged 21-33 years: the ovarian hormone estradiol, known for its neuroprotective properties and the personality trait neuroticism, previously associated with stress sensitivity. Participants completed one night of habitual sleep followed by one night of overnight wakefulness, mimicking a transition from an off- to an on-night shift. Women with higher morning blood estradiol levels or lower neuroticism (indexed by higher emotional stability scores) exhibited non-significant tendencies towards faster reaction times during successful psychomotor vigilance test (PVT) trials, which assess sustained attention. Notably, lower neuroticism was also associated with significantly fewer attentional lapses (reaction times ≥ 500 ms) during the PVT, whereas estradiol levels were not. However, neither trait modulated the overall decline in attentional performance observed following the night-shift condition. In contrast, higher neuroticism-but not estradiol-predicted elevated morning levels of phosphorylated tau at threonine 181 (p-Tau181), a plasma biomarker associated with Alzheimer's disease-related neurodegenerative processes, after the night shift condition. These findings highlight neuroticism as a psychological factor linked to increased neurobiological sensitivity to overnight wakefulness among women.