A high-fat diet regulates Alzheimer-related gene expression in mice, suggests new study

A PLOS ONE study has found a high-fat oriented dietary intervention to be a major factor in the genetic expression of a specific set of proteins that transport fats in the body called Apolipoproteins or Apo’s.
Researchers focused on a particular type of Apolipoprotein, ApoE, which has a known link with Alzheimer’s disease.
There are three isoforms of ApoE: E2, E3 and E4, and it’s the combination of the two copies inherited from our mother and father which determines the risk profile for the degenerative disease.
ApoE is a protein, i.e., a sequence of amino acids, and its specific composition is dictated by corresponding DNA on a given gene. Alterations in the DNA code presumably stop the transcribed ApoE-4 protein performing its biological roles as efficiently as the other alleles.
Possession of the defective ApoE-4 allele of Apolipoprotein E over the neutral version ApoE-3 has been linked to higher risk for Alzheimer’s disease. One study showed that carriers of this genotype have up to 20 times the risk of developing Alzheimers disease than non-carriers.
ApoE genotypes are also commonly associated with cholesterol levels and they interact with non-genetic risk factors, like medication, exercise and diet. The ApoE gene variation is especially one of many polymorphisms or alternative phenotypes that contribute to how the body reacts to carbohydrates and metabolise fat.
The presence of an E2 or E4 isoform for example may influence how the body handles a high-carb versus high-fat diet.
The interplay of the Apolipoprotein genotype and diet is not well understood but many research studies have consistently confirmed that E4 carriers benefit most from low-fat, high-carb diets while E2 carriers benefit most from high-fat, low-carb diets.
In this study, researchers have reinvestigated the impact of diet on ApoE levels by feeding ApoE-3 and ApoE-4 genotype specific engineered mice with high-fat or ketogenic diets for five weeks. They then compared the results with a chow-fed control group.
Looking at the effects of the dietary changes on ApoE in the hippocampus, a region of the brain required for learning and memory and is affected early in Alzheimers disease, it appears that a high-fat diet (60% fat, 20% protein, 20% carbohydrate) reduces hippocampal levels in ApoE-3 mice by approximately 50% but caused no change in the ApoE-4 animals. The ketogenic diet (75% fat, 8.6% protein, 3.2% carbohydrate), however, did not affect hippocampal levels of ApoE in any mouse line, which suggests that the effect seen with the high-fat diet is in fact a result of the carbohydrates.
These new findings show that the effectiveness of dietary changes in Alzheimer patients may be affected by ApoE genotype. Further studies should look for other isoform-dependent dietary interventions as prevention strategies for Alzheimer’s disease.
ApoE variants have also been associated with cardiovascular disease, hypertensio, obesity, dyslipidemia, metabolic syndrome and type 2 diabetes.