TASS, citing the press service of the Icahn School of Medicine at Mount Sinai Hospital (ISMMS, USA), reported on the work of American molecular biologists. At ISMMS, they stated that APOE4 not only disrupts neuron function, but also contributes to the formation of pathogenic connective tissue cells in brain vessels.
APOE4 is considered one of the strongest risk factors for Alzheimer’s disease. One copy of this APOE gene variant increases the risk of developing dementia threefold, and two copies increase it 10–12 times.
To understand the mechanism, the scientists grew several three-dimensional brain tissue models from reprogrammed stem cells of healthy volunteers and carriers of Alzheimer’s disease. They then compared how blood vessels, neurons, and supporting brain cells function in these constructs.
Based on the results of the experiments, the researchers concluded that APOE4 changes not only fat and cholesterol metabolism in neurons and supporting cells, but also the activity of pericytes — connective tissue cells in the vessel walls. In the presence of this mutation, pericytes more often than usual turned into myofibroblasts, and this process, according to the authors of the study, helps accumulate beta-amyloid in the vessel walls and other damaged proteins.
Associate professor at the Icahn School of Medicine at Mount Sinai Joel Blanchard said that damage to the brain’s blood vessels is “not just one of the consequences of Alzheimer’s disease, but a biologically active process that is linked to the APOE4 mutation and that can theoretically be reversed”. He called this mechanism a new target for therapy that may slow the accumulation of beta-amyloid and stabilize blood vessels.
Research fellow at the Icahn School of Medicine at Mount Sinai Braxton Schuldt added that suppressing the activity of the TGF-beta signaling pathway may block this process. According to him, this opens the way to new therapies that will protect blood vessels in patients with Alzheimer’s disease and slow the formation of amyloid plaques.
