Sex differences in the trajectories of plasma biomarkers, brain atrophy, and cognitive decline relative to amyloid onset

INTRODUCTION: The factors that influence the progression of Alzheimer's disease (AD) after individuals become amyloid-positive are poorly understood. This study examines how sex influences the longitudinal trajectories of plasma AD and neurodegenerative biomarkers in the years following a person's estimated onset of amyloid-β. METHODS: Linear mixed effects modeling investigated overall and sex-specific longitudinal trajectories of plasma biomarkers, brain volumes, and cognition relative to estimated age of amyloid onset in a cohort of 78 amyloid-positive Baltimore Longitudinal Study of Aging participants (n=45 male; follow-up time: 6.8 years [SD 3.31]). Amyloid status was ascertained with 11C-Pittsburgh compound B (PiB) PET imaging. RESULTS: After amyloid onset, men displayed steeper increases in pTau181, pTau231, and NfL compared to women. In this same period, men demonstrated steeper declines in brain volume and cognitive performance. DISCUSSION: These findings suggest that sex influences the trajectory of AD pathology, neuronal injury, and symptom progression after individuals become amyloid-positive.