Alzheimer’s disease involves the buildup of the amyloid-β (Aβ) protein in the brain. Aβ can misfold and clump into sticky aggregates that are toxic to neurons. One reason for this toxicity is that Aβ oligomers insert into cell membranes and destabilize them. In fact, experiments have shown that soluble Aβ can cause membranes to leak ions and “remodel” without forming obvious holes.

 

My research explores how Aβ interacts with the fats (lipids) and proteins of cell membranes. I recreate simplified model membranes in the lab and sometimes include specific membrane proteins. Using fluorescence microscopy and electrical measurements, I watch in real time as Aβ binds to the membrane and alters its properties. This approach lets us ask how membrane composition and receptors influence Aβ behavior.

 

Key findings include:

 

1. Lipid composition matters: Membranes containing negatively charged lipids (for example, phosphatidylserine) are far more vulnerable to Aβ. In My experiments, even very low levels of Aβ caused aggregation and membrane rupture when these anionic lipids were abundant. This shows that the exact mix of lipids in the bilayer can strongly influence Aβ toxicity.

 

2. Role of the Membrane receptor: CD36 is a fatty-acid receptor found on certain brain immune cells (microglia) that also happens to bind Aβ fibrils. I found that embedding CD36 in the membrane creates “hotspots” for Aβ nucleation. Aβ molecules accumulate around CD36, and this triggers a dramatic rearrangement of the lipids. In other words, identical Aβ binding can either stiffen a plain membrane or cause a complete mixing of lipid domains (ordered and fluid regions) when CD36 is present. This coupling of receptor binding to membrane reorganization likely amplifies the damaging effect of Aβ.

 

3. Blocking Aβ binding: I also test molecules that can interfere with these interactions. For example, the plant compound ursolic acid can reduce Aβ’s binding and aggregation at membranes, counteracting both the basic lipid effect and the CD36-driven amplification. This points toward possible ways to protect membranes from Aβ.

 

Overall, My work reveals the physical factors that govern Aβ–membrane interactions. By combining model membranes, imaging, and electrical assays, I show how specific lipids and proteins (like CD36) can turn molecular Aβ binding into large-scale membrane damage. These insights help explain how cell membranes become compromised in Alzheimer’s disease and may guide new strategies to prevent Aβ toxicity.