One of the primary characteristics of Alzheimer’s is the accumulation of amyloid-beta peptide (A-beta), something that is believed to be toxic to neurons and many other brain cells, and thus a contributor to the underlying cause of Alzheimer’s.

Individuals carrying the ApoE4 gene have a greater risk of developing Alzheimer’s than individuals with other forms of the gene (APoE2 and APoE3). People who carry two copies of the ApoE4 gene have roughly eight to 10 times the risk of getting Alzheimer's than people who do not.

Researchers at University of Rochester Medical Center have found that ApoE4 is the only known genetic risk factor for Alzheimer's that slows down the brain's ability to eliminate amyloid-beta.
 
"Our latest findings help explain one of the major risk factors for Alzheimer's," said Zlokovic, lead researcher. "ApoE4 changes the brain's ability to rid itself of amyloid-beta. It's becoming more and more apparent that the brain's ability to clear out amyloid-beta, through the vascular system and across the blood-brain barrier, is central to the development of Alzheimer's."

The brain uses a molecule called LRP1 to remove amyloid-beta from the brain speedily and efficiently into the body where it can be easily eliminated.

The researchers found that there is another slower and less efficient molecule involved in the elimination of amyloid-beta known as very low-density lipoprotein receptor (VLDLR), which is especially active when amyloid is coupled to ApoE4

The researchers showed that speedy LRP1 is central to removing amyloid-beta when ApoE2 or ApoE3 is involved, with the slower VLDLR picking up some of the slack. But when the form of the gene that puts people at risk, ApoE4, is involved, VLDLR nearly alone is responsible for hauling the amyloid-beta away.

Not only do the ApoE proteins help determine how quickly amyloid-beta is removed from the brain; the proteins actually couple with amyloid-beta in the brain to form sticky complexes. This gunk gathers around cells and is much more difficult to remove from the brain than free-floating amyloid-beta.