Canceling Out APOE Gene Could Treat Alzheimer's: How One Man's Rare Condition Could Open The Door For Much-Needed Alzheimer’s Drugs
More than 20 years ago, a mutation in the APOE gene was identified as the primary risk factor for late-onset Alzheimer's disease, a progressive form of dementia that causes problems with memory, thinking, and behavior. Now, a new study provides evidence to support theories, which suggest one possible treatment for Alzheimer’s patients would be to eliminate the protein from their brains completely.
The study analyzes the case of a very rare occurrence: a California man whose body does not produce any APOE whatsoever, though his brain functions in a completely normal manner as do his eyes, two key locations where the protein is found. “This suggests that functions of APOE in the brain and eye are not essential or that redundant mechanisms exist whereby its role can be fulfilled,” wrote the authors.
Within our bodies, APOE’s job is to package cholesterol and other fats and move them through the bloodstream. (The name of the gene and the protein it produces are both the same: APOE.) The major kinds (or alleles) of APOE gene are called e2, e3, and e4, with the most common being e3, found in more than half of the general population. About 20 percent of people carry APOE4, which is linked to Alzheimer’s.
The study began when a 40-year-old African-American man showed up at the Lipid Clinic, University of California, San Francisco, suffering from severe hyperlipidemia. His condition causes too high a level of lipids in the bloodstream, which usually goes hand in hand with having high cholesterol. He sought treatment at the clinic because the status quo statin medications and fibrate treatments weren’t working to correct his cholesterol levels. After running tests, researchers found he suffers from a very rare condition, which disrupts his body's processing of cholesterol and causes painful growths of fat under the skin. While this condition is often a result of low levels of APOE, this man’s body lacked the protein entirely.
“APOE has a purpose but maybe there are ways to get around that,” Dr. Mary Malloy, director of UC San Francisco and co-author of the study, told Bloomberg. “Maybe another protein can take over.” The authors of an editorial appearing with the study express the idea more succinctly: The lack of neurological damage in this patient “would appear to answer the question of whether apoE is necessary for brain function with a resounding no.” Let the research begin to develop new and more effective drugs for the disease which worsens over time and currently affects more than five million Americans.
Source: Mak ACY, Pullinger CR, Tang LF, et al. Effects of the Absence of Apolipoprotein E on Lipoproteins, Neurocognitive Function, and Retinal Function. JAMA Neurology. 2014.