#395 - Brain lipidology: understanding APOE, cholesterol homeostasis, Alzheimer's disease risk, and the effects of lipid-lowering therapies on brain health | Tom Dayspring, M.D.

Where this was said

How apoB structure influences LDL receptor binding

At 39:08 · chapter starts 39:00

Peter asks Tom to explain precisely how an LDL particle 'docks' with an LDL receptor. Tom describes the receptor-binding domain on ApoB — specific amino acids that create an electrostatic surface charge complementary to the recognition domain on the LDL receptor. Crucially, this conformational alignment is size-sensitive: large or small LDL particles have distorted ApoB conformations that poorly expose the binding domain, explaining why individuals with predominantly small or large LDL particles can have elevated particle counts despite seemingly normal LDL cholesterol. Tom then reveals a recent NIH finding: LDL receptors function as dimers — two receptors pair up like lobster claws and grab two LDL particles simultaneously. He also explains that in the periphery, ApoE on rare LDL particles can also bind the receptor, and that in the brain, the same receptor exclusively handles ApoE-containing particles, reinforcing his call to rename it the ApoB/ApoE receptor.