Brain network topology defines four Alzheimer's subgroups with distinct cascade stages and treatment response

Four reproducible Alzheimer's subgroups identified via brain network topology show distinct biomarker signatures and cognitive trajectories; post hoc analysis found slower decline after amyloid-targeting treatment mainly in the initiation stage.

• Four subgroups reflect sequential molecular transitions: early vulnerability, initiation, amplification, and terminal.
• Post hoc analysis suggests slower cognitive decline after amyloid-targeting therapy mainly in the initiation stage subgroup.
• The Biological Continuum framework captures disease dynamics overlooked by static ATN threshold-based staging.

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