Scientists have long been working to understand the causes of Alzheimer’s disease. Some cases are related to genetics. There can be small changes in gene sequences, some of which have little to no consequence while others have more significant effects. There are variants of one gene called APOE that are known to be related to the risk of Alzheimer’s disease. When a person carries two copies of the APOE4 variant, their risk of Alzheimer’s increases dramatically. Now, scientists have learned more about why the APOE4 variant has this effect. The findings have been reported in Nature Metabolism.
This study found that APOE4 changes the metabolism of brain cells. During aging, cells get less efficient at making energy from glucose. Scientists determined that neurons can begin to metabolize lipids instead in a bid for survival.
"The ability to use glucose diminishes in the aging brain, forcing nerve cells to use alternative sources for energy production. Our research now documents that this alternative energy source is lipids,” explained senior study author Professor Thomas Willnow of Aarhus University.
However, the APOE4 variant blocks this alternative energy production pathway. This finding can also explain why Alzheimer’s is so much more likely as we get older–neurons reach for lipids to survive as a natural part of the aging process, but APOE4 stops them from getting that energy, so the cells die. The brain is “highly dependent,” on this “switch from glucose to lipids,” noted Willnow.
"By using transgenic mouse models and stem-cell-derived human brain cell models, we uncovered that the pathway enabling nerve cells to burn lipids for energy production doesn't work with APOE4, because this APOE variant blocks the receptor on nerve cells required for lipid uptake," Willnow explained.
Worldwide, about 163 million people carry two copies of the APOE4 variant. But these research findings could help scientists find a way to treat or even prevent the disease. And not everyone who carries two APOE4 copies will definitely get Alzheimer’s, so there is no reason to be tested or to panic if one is a carrier.
"We know that a healthy body, to a large extent, equals a healthy brain. Although not proven in patients yet, our data also suggest that providing more healthy lipids for the cells to thrive—especially poly-unsaturated fatty acids in vegetable or fish oil, may help. Even cells that work poorly will function better when given more fuel,” added Willnow.
Sources: Aarhus University, Nature Metabolism