Relationship between Topological efficiency of White Matter Structural Connectome and Plasma Biomarkers across Alzheimer's Disease Continuum

Abstract Background Plasma biomarkers and brain network topology have shown potential in early diagnosing Alzheimer's disease (AD). We sought to explore relationships among plasma biomarkers, white matter structural network efficiency, and cognitive performance along the AD continuum. Materials and Methods This retrospective study evaluated participants from the Sino Longitudinal Study of Cognitive Decline (SILCODE) cohort between September 2009 and October 2022, with available blood samples or 3.0-T MRI brain scans. Plasma biomarker levels were measured using the Single Molecule Array platform, including β-amyloid (Aβ), phosphorylated tau181 (p-tau181), glial fibrillary acidic protein (GFAP), and Neurofilament light chain (NfL). The topological structure of brain white matter was assessed using network efficiency. Trend analyses and mediation analyses were conducted to investigate the relationships among plasma markers, network efficiency, and cognitive performance across the AD continuum. Results 498 participants along the AD continuum (mean age, 67.7 years ± 6.7 [SD]; 172 women) were included: 192 with subjective cognitive decline (SCD), 58 with mild cognitive impairment (MCI), 25 with AD, and 223 controls. The study involved 287 blood samples and 395 brain scans. GFAP was the most sensitive marker (t = 11.164, p = 3.59×10 − 24 ), followed by NfL (t = 6.542, p = 2.9×10 − 10 ), p-tau181 (t = 8.452, p = 1.61×10 − 15 ) and Aβ42/Aβ40 (t=-3.257, p = 1.27×10 − 3 ). Local efficiency decreased in the frontal, temporal cortex, and striatum. The principal component of local efficiency within these regions correlated with GFAP (r = − 0.61, p = 6.3×10 − 7 ), NfL (r = − 0.57, p = 6.4×10 − 6 ), and p-tau181 (r = − 0.48, p = 2.0×10 − 4 ). Network efficiency mediated the relationship between cognition and GFAP (β=-0.224, p = .0196) or NfL (β=-0.346, p = .0188). Conclusions Network efficiency mediates the association between plasma biomarkers (especially GFAP and NfL) and cognitive performance along the AD continuum. These findings contribute to understanding AD pathogenesis and may have implications for early diagnosis and intervention.