The role and mechanisms of neural circuit damage and repair in the onset and recovery of Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by progressive cognitive decline rooted in structural and functional impairment of neural circuits. The dynamic mechanisms governing circuit pathology and repair in AD remain elusive. In this article, the injury mechanisms within core AD circuits (e.g., hippocampo-entorhinal and Papez circuits) were systematically illustrated, highlighting the advances in their repair and reorganization. Beyond summarizing the Aβ/Tau pathology-circuit dysfunction interaction, the hypothesis that circuit abnormalities precede protein deposition was also critically examined. Furthermore, the potential and challenges of circuit-targeted interventions (e.g., neuromodulation, etc.) in the treatment of AD were evaluated. We advocate for a precision therapeutic paradigm focused on circuit remodeling to effectively slow disease progression and promote recovery. This work provides a theoretical framework for AD circuitopathy and guides the development of targeted therapies.