One of the hallmarks of the brain of an individual with Alzheimer disease is the accumulation of amyloid-beta peptide (A-beta), something that is believed to be toxic to many brain cells (specifically neurons) and to therefore contribute to the underlying cause of disease.

Berislav Zlokovic and colleagues, at the University of Rochester Medical School, have now generated data in mice that mechanistically links a genetic risk factor for Alzheimer disease with accumulation of A-beta in the brain.

Individuals carrying one form of the APOE gene, APOE4, have a greater risk of developing Alzheimer disease than individuals with other forms of the APOE gene (APOE2 and APOE3).  APOE's official name is apolipoprotein E because it provides instructions for making the protein called apolipoprotein E.  It is a lipoprotein because it combines with lipids and is responsible for packaging cholesterol and other fats, carrying them through the bloodstream, and delivering them to the appropriate locations in the body for use.  It has at least alleles - E2, E3, and E4. The most common allele is E3, which is found in more than half of the population.

In the study, the proteins generated by the different forms of the APOE gene were found to differentially affect the clearance of A-beta from the brain of mice. Specifically, A-beta binding to apoE4 led to substantially slower clearing of A-beta from the brain than A-beta binding to either apoE2 or apoE3.

The authors therefore suggest that a decreased rate of A-beta clearance from the brain might contribute to the increased risk of developing Alzheimer disease observed for individuals carrying the APOE4 form of the APOE gene.