Molecular brain changes linked to APOE4 :Study

Recent research has revealed a lot about Alzheimer's disease, but scientists have yet to paint a complete picture of how genetic risk for the illness causes brain damage that ultimately causes memory loss and cognitive decline.

A new study from the Keck School of Medicine, recently published in the Journal of Experimental Medicine documents, in real-time, that APOE4, the main susceptibility gene for Alzheimer's disease, leads to molecular changes in the brain's blood vessels, which are then followed by changes in the synapses that connect brain cells. The study also suggests potential targets in blood vessels for treatment early in the disease process - before cognitive decline occurs.

To study the effect of the APOE4 gene on the brain, the researchers studied "knock-in" mice, where the mouse APOE gene was replaced with human APOE gene variants. To determine the impact the APOE4 gene has on the blood-brain barrier and neurons, the researchers used transcriptomic studies, which focus on the activity of RNA molecules, and proteomic studies, to study the activity and composition of proteins. They also collected behavioral data to measure changes in memory and other cognitive functions. The team first detected damage to endothelial cells, which make up the blood-brain barrier and regulate which substances can enter and leave the brain, and pericytes, which line the blood-brain barrier's walls and help keep it healthy.

Ref:

Berislav Zlokovic et al,A 'multi-omics' analysis of blood-brain barrier and synaptic dysfunction in APOE4 mice,Journal of Experimental Medicine,10.1084/jem.20221137