Multi‐omics delineate growth factor network underlying exercise effects in an Alzheimer's mouse model

• DOI: 10.1002/alz.70024
• Publication Date: 2025-03-31T08:27:08Z
• Authors: Xin Li; Chaozhong Liu; Wenbo Li; Guantong Qi; Yanwan Dai; Chaohao Gu; Yuxiang Sun; Wenjun Zhou; Veronica C. Cilib...; Jing Liang; Udhaya Kumar S; Dongyin Guan; Zhaoyong Hu; Hui Zheng; Zhandong Liu; Hu Chen; Ying‐Wooi Wan; Zheng Sun
• Keywords: Omics

Abstract INTRODUCTION Physical exercise is a primary defense against age‐related cognitive decline and Alzheimer's disease (AD). METHODS We conducted single‐nucleus transcriptomic chromatin accessibility analyses (snRNA‐seq snATAC‐seq) on the hippocampus of mice carrying mutations in amyloid precursor protein gene (APP NL‐G‐F ) following prolonged voluntary wheel‐running exercise. RESULTS Exercise mitigates amyloid‐induced changes transcriptome through cell type–specific regulatory networks converging growth factor signaling, particularly epidermal receptor (EGFR) signaling. The beneficial effects neurocognition can be blocked by pharmacological inhibition EGFR its downstream PI3K leads to elevated levels heparin‐binding EGF (HB‐EGF), intranasal administration HB‐EGF enhances memory function sedentary APP mice. DISCUSSION These findings offer panoramic delineation hippocampal transcriptional activated suggest signaling as druggable contributor exercise‐induced enhancement combat AD‐related decline. Highlights snRNA‐seq snATAC‐seq analysis after wheel‐running. counteracts changes. Networks converge activation insulin Pharmacological benefits Intranasal