The Transformation: From Support to Scarring

A research team lead by Joel Blanchard, PhD, is investigating the causes of Alzheimer's disease and screening for new therapies.

Dr. Blanchard’s research group uses human stem cell-derived "mini-brain" models that allow for analyses of human brain function. In a recent study published as a preprint in bioRxiv, Dr. Blanchard and his collaborators investigated the effects of Alzheimer's disease on cells known as pericytes, which normally wrap around blood vessels to maintain their integrity and regulate blood flow.

In carriers of the APOE4 gene, these essential cells undergo a pathological shift: the number of healthy pericytes drops significantly, leaving blood vessels vulnerable. In their place, a new population emerges: "myofibroblast-like" cells that act more like scar-tissue producers than vascular supports. These rogue cells secrete fibronectin, a sticky protein that acts as a scaffold, catching and anchoring amyloid within vessel walls and accelerating disease progression.

The Driving Mechanism: TGF-β

The study identified a specific signaling pathway, TGF-β, as the primary driver of this cellular identity crisis. In the presence of APOE4, TGF-β signals instruct protective pericytes to transform into damaging myofibroblasts.

A New Path for Treatment

The most promising finding involves the reversal of this process. By inhibiting the TGF-β signal in experimental models, researchers were able to restore healthy pericyte coverage, eliminate scarring, and reduce vascular amyloid levels to those found in lower-risk APOE3 brains.

This discovery identifies a clear, targetable biological switch that could lead to new therapies designed to protect the brain's blood supply and slow the onset of Alzheimer's pathology.