Scientists Identify ERBB4 as Key Switch Driving Alzheimer’s Progression
Creatrip Team
23 days ago
Researchers at the Institute for Basic Science (IBS) discovered that the protein ERBB4 acts as a central “switch” that accelerates Alzheimer’s disease. Single‑cell RNA sequencing in mouse brains revealed a group of early‑responsive excitatory neurons (EREN) with abnormal gene expression. Network analysis highlighted ERBB4 from a ‘turquoise module’ as a critical regulator. Selectively suppressing ERBB4 in excitatory neurons of Alzheimer’s model mice restored excitatory/inhibitory balance, reduced brain inflammation, and cut toxic amyloid‑beta deposits by over 50%, leading to improved memory and spatial navigation. Conversely, increasing ERBB4 in normal mice reproduced Alzheimer‑like pathology. Analysis of human brain transcriptome data from 446 Alzheimer’s patients showed higher ERBB4 levels correlate with more amyloid accumulation and worse cognition. The team proposes ERBB4 as a promising therapeutic target that could break the vicious cycle of inflammation, synaptic imbalance, and toxic protein buildup. (EREN: early responsive excitatory neurons)
