Although the brain is the organ with the highest cholesterol content, almost all of the cholesterol in the brain is actually synthesized in the brain; high levels of cholesterol can be a risk factor for Alzheimer’s disease. An enzyme called ACAT in the cholesterol pathway can increase production of amyloid, resulting in the buildup of amyloid plaque bundles in the brain. A mechanism of action was identified called palmitoylation that accounts for the relationship between ACAT and increased toxic production of amyloid plaques. Further studies have revealed that ACAT inhibitors reduced brain cholesterol in the lab, but also led to increased incidence of stroke and heart attack. 

Dora Kovacs, Ph.D., Massachusetts General Hospital