Beyond binary classification: Comparing three region-based multi-phase Aβ staging systems.

INTRODUCTION

This study aims to establish a multi-phase visual staging system based on amyloid-beta (Aβ) deposition to more precisely assess the stages of Aβ accumulation in Alzheimer's disease (AD), and to validate the cognitive function, neurodegeneration, and blood biomarker characteristics at different stages.

METHODS

A total of 1002 participants from the Chinese Preclinical Alzheimer's Disease Study (C-PAS) cohort were included. Aβ deposition was assessed using positron emission tomography (PET) imaging, and three multi-phase Aβ deposition grading systems were established. Participants underwent neuropsychological testing, peripheral blood biomarker collection, and multimodal neuroimaging data acquisition.

RESULTS

Cognitive function, peripheral blood biomarkers, default mode network (DMN) function, and hippocampal volumes showed stage-dependent changes across different Aβ deposition stages. Different grading systems revealed varying clinical manifestations and biomarker sensitivity.

DISCUSSION: Region-based multi-phase Aβ deposition systems demonstrate practical utility in detecting early pathological changes, understanding disease progression, and informing early diagnosis and intervention strategies for AD.

HIGHLIGHTS: Developed and validated visual multi-phase Aβ deposition staging systems for AD progression. Revealed stage-specific cognitive, neurodegenerative, and biomarker characteristics in AD. Demonstrated the sensitivity of visual methods to detect early, regional Aβ deposition. Highlighted differential strengths of Villeneuve, Grothe, and Mattsson staging systems. Proposed multi-phase systems as tools for personalized AD diagnosis and intervention strategies.