Researchers Identify ERBB4 Shift as Possible Trigger of Alzheimer's

Scientists at the Institute of Basic Science in South Korea discovered that the ERBB4 receptor, typically found in neurons that dampen brain activity, is abnormally expressed in excitatory neurons during the initial stages of Alzheimer's disease. This misplacement appears to trigger multiple disease hallmarks, including neuronal hyperactivity, glial imbalance, and plaque accumulation. Gene-editing removal of ERBB4 from excitatory hippocampal neurons in mouse models quieted overactive cells, lowered astrocyte and microglia reactivity, reduced amyloid plaques, and restored performance on memory and spatial tests.

Conversely, activating ERBB4 in a few healthy neurons induced excessive activity and cognitive deficits. Examination of post-mortem tissue from about 450 individuals confirmed higher ERBB4 levels in excitatory neurons of Alzheimer's patients, highlighting it as a potential therapeutic target.