Plasma biomarkers as core mediators in functional network abnormalities: Evidence from a two-cohort study

Area of Science:

• Neuroscience
• Biomarker Research
• Neuroimaging

Background:

• Established association between amyloid beta (Aβ) deposition, tau pathology, and disruptions in brain functional networks.
• Unclear role of plasma biomarkers in mediating these relationships.

Purpose of the Study:

• To investigate the mediating role of plasma biomarkers in the relationship between Aβ deposition and functional network alterations.
• To explore underlying pathways connecting Aβ pathology, plasma biomarkers, and brain connectivity.

Main Methods:

• Analysis of plasma biomarkers, amyloid beta positron emission tomography (PET), and resting-state functional magnetic resonance imaging data from 348 participants across two cohorts (SILCODE and ADNI).
• Assessment of correlations between plasma biomarkers, functional connectivity, and global Aβ standardized uptake value ratio (SUVR).
• Mediation analysis to identify pathways linking Aβ PET SUVR, plasma biomarkers, and functional networks.

Main Results:

• Significant correlations were found between plasma biomarkers (p-tau181, p-tau217, NfL, GFAP, Aβ42/40) and global SUVR and functional connectivity.
• Functional connectivity variations across different brain networks were observed across Aβ stages, mediated by plasma biomarkers.
• A key pathway identified: Aβ PET SUVR → plasma biomarkers (p-tau181, p-tau217) → functional networks, with fully mediated effects.

Conclusions:

• Plasma biomarkers, particularly p-tau181 and p-tau217, play a central mediating role in Aβ accumulation and functional network alterations.
• These findings highlight the potential of plasma biomarkers for tracking Alzheimer's disease progression, identifying pathological changes, and enabling early disease detection across diverse populations.