High-fat diet in utero protects against Alzheimer's

A high-fat diet can carry health risks, but for mothers-to-be, it may make all the difference when it comes to Alzheimer's disease prevention for their children, according to new research published in the journal Molecular Psychiatry.

Researchers at the Lewis Katz School of Medicine at Temple University found in animals that high maternal fat consumption during gestation protects offspring against changes in the brain that are characteristic of late-onset Alzheimer's disease.

Genetic factors transmitted by mothers to their offspring seem like an obvious explanation behind this phenomenon, but so far no genes have been identified that could explain the maternal transmission of Alzheimer's disease. This fact would suggest that environmental factors, such as lifestyle and diet, adopted during the gestation period, a time in which mother and baby are in tight interaction, could significantly influence the offspring's risk of developing the disease later in life.

Diet is of particular interest as a risk factor, especially a diet rich in animal fat and cholesterol. High-fat intake previously has been shown in young/adult mice to directly exacerbate the types of changes in brain function that ultimately may contribute to Alzheimer's disease.

To better understand the unique relationship between maternal Alzheimer's disease and risk in her offspring, researchers led by Domenico Praticò, MD, director of the Alzheimer's Center at Temple University, 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 from the beginning until the end of gestation. The moment offspring were born, mothers were switched to a regular diet, which was maintained during the lactation period. Offspring of these mothers were always kept at the same regular, or standard, diet throughout their life.

At 11 months of age, offspring underwent behavioral tests to assess learning ability and memory. The observed improvements in memory and learning were associated with the maintenance of good synaptic integrity. 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. Synapses, the places where neurons come together to relay information, play a vital role in learning and memory formation, according to the study abstract.

In addition, compared to animals born to mothers fed a regular diet, offspring from mothers on a high-fat diet had lower levels of amyloid-beta, an abnormal protein that builds up in neurons, contributing to nerve cell dysfunction and eventually significant 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. The researchers found that already 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. They demonstrated that the repressive activity of FOXP2 on these genes ultimately 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," said Praticò. "Diet at this specific life stage can have critical, but underestimated, long-term impacts on brain health."