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Animals born to mothers fed a high-fat diet during gestation were protected against brain changes characteristic of late-onset Alzheimer’s disease, according to a study published by researchers at the Lewis Katz School of Medicine at Temple University. The study holds implications for humans, as previous research has shown that individuals whose mothers develop Alzheimer’s disease after age 65 are at increased risk of also developing the disease around the same age.

Although genetic factors may seem to play a role in the development of Alzheimer’s, no genes have thus far been identified, suggesting that environmental factors, such as lifestyle and diet adopted during gestation, could significantly influence risk. To better understand the unique relationship between maternal Alzheimer’s disease and risk in offspring, Domenico Praticò and colleagues looked at maternal fat intake specifically during the gestation period in mice engineered to develop Alzheimer’s disease.

Pregnant mice were fed a high-fat diet throughout gestation, and after offspring were born, mothers were switched to a regular diet, which was maintained during the lactation period. Offspring of these mothers were kept on a standard diet throughout their life. At 11 months of age, offspring underwent behavioral tests to assess learning ability and memory. “Surprisingly, we found that animals from mothers fed a high-fat diet during gestation had better learning and memory skills than their counterparts born to mothers fed a regular diet during gestation,” said Praticò.

The observed improvements in memory and learning were associated with the maintenance of good synaptic integrity. In fact, offspring from mothers exposed to a high-fat diet had significant improvement of synapse function when compared with offspring from mothers on a regular diet. They also had lower levels of amyloid-beta, an abnormal protein that builds up in neurons, contributing to nerve cell dysfunction and impairments in memory and learning.

When the team searched for possible mechanisms responsible for the beneficial effect, they discovered that offspring from mothers fed a high-fat diet exhibited reduced levels of three important genes involved in Alzheimer's disease: beta-secretase, tau, and the pathological tau-regulating gene CDK5. In the early developmental stages, the three genes were effectively switched off in offspring because the high-fat diet had increased activity of a protein called FOXP2, which protected offspring from later declines in brain function and Alzheimer’s disease development.

“Our findings suggest that, to be effective, Alzheimer’s disease prevention probably needs to start very early in life, during gestation,” observed Praticò. “Diet at this specific life stage can have critical, but underestimated, long-term impacts on brain health.”

The researchers plan to compare the effects of a high-fat diet to those of other diets, including high-sugar, high-protein, and a diet similar to the Mediterranean diet in humans.

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