A team of scientists has found that the presence of the APOE4 protein – the most important genetic risk factor for Alzheimer’s disease – can cause healthy immune cells – microglia – in the brain to cause harmful inflammation and clumps of misfolded proteins.
The same microglia, in the brain without the APOE4 protein, patrol for damage and remove debris and harmful proteins.
For the study, scientists at the Gladstone Institute in the US created a “chimeric” mouse model to study Alzheimer’s. Not only did the mouse model carry human APOE genes, but the team also transplanted human neurons producing the APOE4 protein into the mice’s brains.
Upon removing the microglia, they discovered that the APOE4 protein no longer triggered as many deposits of amyloid or tau—two types of misfolded proteins that are hallmarks of Alzheimer’s disease.
The findings, published in the journal Cell Stem Cell, suggest that drugs that can reduce APOE4 levels in neurons or target microglia — either by reducing the number of microglia or by reducing their level of inflammatory activity — could slow a A promising strategy may be to prevent the development of Alzheimer’s disease in people with the APOE4 gene.
“Drugs that reduce microglia (in Alzheimer’s patients) may eventually be useful in treating the disease,” said Gladstone senior investigator Yadong Huang.
Importantly, the team transplanted the neurons into the mice model, after the brain had matured. This helped researchers mimic late-onset Alzheimer’s disease.
