Older adults carrying a specific genetic variation linked to Alzheimer’s disease might actually protect their brain health by eating a diet high in meat. A recent study published in JAMA Network Open suggests that personalized dietary recommendations based on genetics could help prevent cognitive decline in a large portion of the global population.
Every person carries a gene called APOE, which provides instructions for making a protein that helps carry fats and cholesterol through the bloodstream. This gene comes in three main versions, known as variants, named e2, e3, and e4. A person inherits one variant from each parent, creating different genetic combinations. Apolipoproteins are a family of proteins that bind to fats, playing a major role in cholesterol metabolism in the liver and the brain.
The APOE e4 variant is the oldest form of the gene in human evolutionary history. It first appeared millions of years ago, around the time our early ancestors transitioned to hunting and began consuming large amounts of meat. Some anthropologists propose that human ancestors went through a period a few million years ago where they consumed diets made up almost entirely of meat. This timeline aligns directly with the emergence of the APOE e4 variant.
The newer variants, e3 and e2, emerged much later in human history. Human populations eventually shifted toward agriculture and started eating more plant-based foods. The e3 variant is thought to have appeared roughly 200,000 years ago, reflecting an adaptation to an omnivorous diet. Today, the e3 variant is the most common form found across global populations.
In modern times, the APOE e4 variant is the strongest known genetic risk factor for late-onset Alzheimer’s disease. People who inherit copies of this variant have a much higher chance of developing dementia compared to those with other combinations. In Northern Europe and North America, individuals with the e3/e4 or e4/e4 combinations account for nearly 70 percent of all Alzheimer’s cases.
Researchers at the Karolinska Institute in Sweden wanted to understand how dietary habits interact with these genetic risks over time. Lead author Jakob Norgren, a researcher at the institute’s Department of Neurobiology, Care Sciences and Society, suspected that our evolutionary history might hold clues. He and his colleagues hypothesized that the older APOE e4 variant might be specifically adapted to a high meat diet.
If this idea held true, people with the older gene variants might process animal nutrients differently than people with the newer variants. “This study tested the hypothesis that people with APOE 3/4 and 4/4 would have a reduced risk of cognitive decline and dementia with higher meat intake, based on the fact that APOE4 is the evolutionarily oldest variant of the APOE gene and may have arisen during a period when our evolutionary ancestors ate a more animal-based diet,” says Norgren.
To investigate this potential connection, the research team analyzed data from an ongoing project called the Swedish National Study on Aging and Care. They focused on a specific group of 2,157 older adults living in an urban area of Stockholm. All the participants were at least 60 years old and free of any dementia diagnosis when the study began.
The volunteers provided detailed information about their dietary habits through validated questionnaires. These forms covered 98 different food items, capturing the participants’ eating habits over the previous year. The research team grouped the volunteers based on their daily intake of total meat, unprocessed red meat, poultry, and processed meats like sausage or bacon. They also drew blood samples to determine each participant’s APOE gene combination.
Over a period of up to 15 years, the researchers tracked the cognitive health of the volunteers. Participants were evaluated every six years until they reached age 78, and then every three years after that. At each visit, doctors assessed memory, language skills, and mental processing speed. Two independent physicians reviewed the medical data to diagnose any cases of dementia, with senior neurologists stepping in if there were any disagreements.
The researchers separated the data into two main groups based on genetics. One group included people with the e3/e4 and e4/e4 combinations, which carry a high risk for Alzheimer’s disease. The second group consisted of people with all other gene combinations. They compared the cognitive trajectories of both groups against their self-reported meat consumption.
A clear pattern emerged for individuals with the high risk e3/e4 and e4/e4 genes. For this group, eating more meat was associated with slower cognitive decline and better memory preservation. The protective association was strongest for those in the top twenty percent of meat consumption.
These high consumers ate an average of about 870 grams of meat per week, standardizing the measure to a typical daily intake of 2,000 calories. Within this high consumption group, the expected genetic vulnerability vanished entirely. Their rates of cognitive decline mirrored those of people without the high risk gene variants.
The research team did not observe any similar benefits from meat consumption for people carrying the newer gene variants. In fact, people with the high risk gene combinations who ate the least amount of meat faced more than twice the risk of developing dementia compared to people without those gene variants. This suggests that a low meat diet might trigger the genetic vulnerability associated with the older genetic variant.
“There is a lack of dietary research into brain health, and our findings suggest that conventional dietary advice may be unfavourable to a genetically defined subgroup of the population,” says Norgren. “For those who are aware that they belong to this genetic risk group, the findings offer hope; the risk may be modifiable through lifestyle changes.”
The type of meat consumed played a defining role in the health outcomes. Unprocessed meats were associated with better brain health and lower mortality rates in the high risk genetic group. However, processed meats failed to offer these protective benefits.
“A lower proportion of processed meat in total meat consumption was associated with a lower risk of dementia regardless of APOE genotype,” says Sara Garcia-Ptacek, an assistant professor at the Karolinska Institute and a senior author of the study. Eating processed foods appears detrimental to cognitive health across all genetic backgrounds.
The researchers also looked into possible biological mechanisms to explain their observations. They measured blood levels of certain vitamins, finding that people with the e4 gene variants seemed to absorb vitamin B12 from meat better than those with other variants. This hints that the older genetic profile might be uniquely tuned to extract nutrients from animal products.
The study has several limitations that require consideration. It was an observational study, meaning the researchers tracked natural habits rather than assigning specific diets, making it impossible to prove cause and effect. The participants also self-reported their food intake, a method that occasionally introduces memory errors into the data.
Additionally, the study population was predominantly of Northern European descent. Because the APOE gene behaves differently in various ethnic populations, these associations might not apply globally. For instance, the increased Alzheimer’s risk associated with the e4 variant is known to be weaker in Hispanic and Black populations compared to white populations.
Future research will need to address these gaps through controlled clinical trials. Scientists must directly test whether increasing unprocessed meat intake can actively prevent dementia in people with specific high risk gene combinations. “Clinical trials are now needed to develop dietary recommendations tailored to APOE genotype,” says Norgren.
Such trials could eventually lead to personalized nutrition plans that protect the aging brain based on an individual’s evolutionary genetic makeup. “Since the prevalence of APOE4 is about twice as high in the Nordic countries as in the Mediterranean countries, we are particularly well suited to conduct research on tailored dietary recommendations for this risk group,” Norgren continues.
The findings highlight the growing relevance of precision nutrition in cognitive aging research. The study, “Meat Consumption and Cognitive Health by APOE Genotype,” was authored by Jakob Norgren, Adrián Carballo-Casla, Giulia Grande, Anne Börjesson-Hanson, Hong Xu, Maria Eriksdotter, Erika J. Laukka, and Sara Garcia-Ptacek.
