Untangling The Alzheimer's Brain

Alzheimer’s is a debilitating disease where circuits in the brain literally get ‘tangled up’ and cause cognitive problems. Research into the causes and possible treatments for Alzheimer’s is intensive and beginning to provide rays of hope for families hit with this disorder.

The Triple Threat

One tool that researchers have used extensively is a mouse model, which is genetically destined to get Alzheimer’s disease due to three separate genes. There are several paths to Alzheimer’s, but having a gene that increases your risk for getting the disease does not guarantee you will get it. It still depends on many lifestyle factors, including your physical activity, nutrition and level of physical health. However, the Alzheimer’s mouse model, called the 3xTg-AD mouse, has the deck stacked against it with multiple genes increasing its risk and almost guaranteeing disease.

A couple of recent studies used these mice to look at the role of some specific dietary factors in helping or hurting the mice’s chances. The first study looked at low omega-3 to omega-6 ratios in the context of a low or high fat diet. The second study used vitamin B3 (nicotinamide) to try and counter some of the cognitive problems the mice develop as Alzheimer’s progresses.

Fish for Brains

Julien et al. from Lavel University in Quebec published a study in the Neurobiology of Aging, in which they reported a double whammy of low omega-3s and high fat that seems to make the genetically susceptible mice fair worse. Unfortunately, the diet they discovered as further increasing Alzheimer’s risk is not that different from what most westerners are eating.

Many folks in North America eat too much saturated fat and not enough good omega-3 fat from fish. When researchers gave this kind of diet to the Alzheimer’s mice, the brains of the mice had several increased markers of Alzheimer’s pathology. In teasing out the dietary problems, researchers found that either a high fat diet or a diet low in omega-3s, caused problems. When they combined the two, feeding low omega-3s in the context of a high fat diet, those problems compounded.

These data are consistent with previous observational studies in humans that show people who eat less omega-3s have increased rates of Alzheimer’s disease. Unfortunately, studies have not shown success of using omega-3 supplementation to treat Alzheimer’s once it takes hold. However, there has been some success in treating early mild dementia. These studies, along with the new data from mice suggest that we should get plenty of omega-3s into our diet earlier to help drive down the risk of Alzheimer’s later.

Vitamin B3 gets an A

Still, there may be good news on the Horizon for those who are already heading down the Alzheimer’s road. Green et. al. from UC-Irvine published a study in the Journal of Neuroscience that demonstrated some remarkable effects of vitamin B3 at protecting the genetically prone mice from getting Alzheimer’s.

Now, before you rush out and start dosing up, realize this is a preliminary study that used whopping amounts of vitamin B3. Researchers fed mice at about 100 times the RDA and at about 10 times doses previously shown to cause some toxicity in humans. Still, the study is promising because it helps reveal some ways in which we might approach preventing Alzheimer’s disease in high-risk populations.

Researchers dosed up the 3xTg-AD mice with large amounts of nicotinamide, an active form of vitamin B3, in their drinking water. These mice performed as well as normal mice on many memory and other cognitive tests. Conversely, the Alzheimer’s prone mice that didn’t get the vitamin B3 showed the expected cognitive decline associated with Alzheimer’s.

Food Matters

The cool thing about both of these studies is that they open the door for more research using nutritional approaches to treat and prevent Alzheimer’s disease. It’s clear that genetics plays a role in some, but not all cases of dementia. But it’s also clear that we don’t have to accept our genetic predispositions in many cases. It is not fate. They way we choose to live our lives, including what we choose to eat, will play a large role in our cognitive future.

References:
Journal of Neuroscience (2008), 28(45): 11500-11510.
Neurobiology of Aging (2008), In Press.