Alzheimer’s Advance: Omega-3 fatty acid benefits mice

A diet that includes a key omega-3 fatty acid found in fish and canola oil prevents some memory loss in mice that develop a disease similar to Alzheimer’s, researchers report in the Sept. 2 Neuron.

The finding is consistent with previous research suggesting that fish oil supplements might reduce the risk of Alzheimer’s disease in people. Other work has shown that the fatty acid, called docosahexaenoic acid (DHA), is essential to brain function and that Alzheimer’s patients have low concentrations of it in their blood.

The early memory and learning problems that mark the disease occur because damaged brain cells fail to transmit messages consistently to each other across junctions called synapses.

To assess what role DHA might have in maintaining this transmission, Greg M. Cole, a neuroscientist at the University of California, Los Angeles (UCLA) and his colleagues used old mice—17 months on average—that were genetically engineered to develop waxy protein plaques in their brains, much as Alzheimer’s patients do.

Some mice received food without DHA for 103 days and subsequently showed depleted stores of DHA in their brains. In contrast, mice getting chow supplemented with DHA had high brain concentrations of the fatty acid. Notably, these animals maintained good concentrations of two proteins that enable synapses to function, but DHA-deficient mice had insufficient concentrations of those substances.

Commenting on the study, nutritionist Julie A. Conquer of the University of Guelph in Ontario says that these results show that DHA in the diet can affect the biochemistry of brain-signaling pathways.

Cole and his team also tested memory in elderly mice that had received food with or without DHA for nearly 5 months. They trained the 21-month-old mice to swim to a platform in a tank of warm water, then raised the water level to submerge the platform slightly. Because the platform was no longer directly visible, the mice had to remember where it was, on the basis of visual clues positioned around the tank.

After a week of practice, the mice getting DHA took 20 to 30 seconds to find the hidden platform. Their counterparts not receiving DHA took 50 seconds or more. Some mice in the latter group didn’t appear to recall where the platform was at all, swimming around the edge of the tank until being fished out, says study coauthor Sally A. Frautschy, a neurobiologist at UCLA. She adds that normal mice, once trained, can find the hidden platform in about 10 seconds.

“This is spatial memory, like trying to remember where you parked your car,” she says. “That’s memory you lose in Alzheimer’s disease.”

Conquer says that research into omega-3 fatty acids in Alzheimer’s disease is now taking two tracks. Studies on the biological track, which include the new work by Cole and his colleagues, seek to clarify how the fatty acids affect brain function. The other research approach centers on monitoring the course of disease in newly diagnosed Alzheimer’s patients taking or not taking fatty acid supplements.

Among the outstanding questions is the role of the waxy plaques, made of the short protein amyloid beta, in Alzheimer’s. Cole hypothesizes that an accumulation of the substance causes oxidative damage to DHA.