Fall 2025 Grantee Highlight:
Jinchong Xu

Jinchong Xu, PhD

Assistant Professor of Neurology, Director, Human iPSC for Neurodegenerative Disease Research, Johns Hopkins Alzheimer’s Disease Research Center,
Johns Hopkins School of Medicine

The Xu Lab is advancing a new framework for understanding Alzheimer’s disease, one that looks beyond the late-stage buildup of amyloid plaques and tau tangles to the earlier breakdown of neural circuit function. Their work focuses on NPTX2, a synaptic organizer that helps maintain the balance between excitatory and inhibitory neurons, a balance essential for stable communication across brain networks. Since NPTX2 levels fall years before symptoms appear, its decline may represent one of the earliest disruptions that predispose the brain to cognitive deterioration.

To investigate this early vulnerability, the Xu Team has developed human iPSC-derived cortical networks with precisely tuned neuronal equilibrium, as well as next-generation forebrain organoids that incorporate immune and vascular components. These systems allow direct measurement of synaptic strength and network rhythms as NPTX2 levels change. Their findings show that NPTX2 loss results from a regulatory shutdown in which cells fail to activate the gene and produce the protein, rather than from permanent genetic alterations. By uncovering the mechanisms that silence this resilience pathway, the Xu Lab aims to design targeted interventions that restore NPTX2 expression and reinforce neural circuits before degeneration becomes irreversible.