Relationship between topological efficiency of white matter structural connectome and plasma biomarkers across Alzheimer’s disease continuum

Introduction The associations between plasma AD biomarkers, brain network topology, and cognition across AD continuum remained unknown. Methods From the cohort of Sino Longitudinal Study of Cognitive Decline, we analyzed plasma biomarkers of 287 participants, including the levels of β-amyloid (Aβ), phosphorylated-tau181 (p-tau181), glial-fibrillary-acidic-protein (GFAP), and neurofilament-light-chain (NfL), and we assessed white matter network efficiency of 395 participants. Trend analyses evaluated the sensitivity of plasma markers and network efficiency with AD progression. Correlation and mediation analyses further explored the relationships among plasma markers, network efficiency, and cognition across AD continuum. Results Among the plasma markers, GFAP exhibited the highest sensitivity with AD progression, followed by NfL, p-tau18, and Aβ42/Aβ40. Local efficiency decreased in multiple brain regions and correlated with GFAP, NfL, and p-tau181. Network efficiency mediated the relationship between plasma markers and cognition. Discussion Our findings highlight the potential of network-plasma approaches for early detection and intervention of AD.