New research led by Yuxi Liu, a scientist at Brigham and Women’s Hospital and Harvard Medical School, once again confirms that our health, including the condition of our brains, is the result of a complex interplay between genetics, lifestyle, and metabolism. This important paper, published in the journal Nature Medicine in 2025, provides a completely new explanation of how the genome, blood metabolites, and diet affect the risk of Alzheimer’s and other forms of dementia.
Alzheimer’s disease and related dementia cause a decline in cognitive function in millions of people. Although genetics, especially the APOE4 gene, plays a crucial role in the development of these diseases, new research shows that genetics is not the only determining factor.
As part of this study, scientists analyzed data from more than 4,200 women and nearly 1,500 men after 34 years of observation. They studied the participants’ genetics, blood metabolite profiles, and how closely they adhered to the Mediterranean diet. This eating plan, which is rich in fruits, vegetables, and healthy fats, has long been known for its beneficial properties for brain health.
The research focused mainly on APOE4 homozygotes (people who have two copies of the APOE4 gene). A unique metabolic profile was found in this group that was associated with a high risk of dementia.
It was found that a high level of lipid metabolites (cholesterol esters and sphingomyelins) in the blood increased the risk of dementia. This result points to a disorder in cholesterol metabolism and inflammatory processes in the brain. In contrast, glycerides reduced the risk of dementia. This means that they may be able to protect the brains of APOE4 gene carriers from the accumulation of harmful proteins.
The study highlights betaine as an important metabolite involved in cellular metabolism. It was found that a high level of betaine increased the risk of dementia only in APOE4 homozygotes, which indicates a disorder related to neuroinflammation. Scientists also found that compounds linked to glutamine and GABA protected the brain from dementia. This result suggests that changes in the balance of neurotransmitters also play a significant role in the development of the disease.
Scientists determined that the Mediterranean diet caused metabolic changes: the levels of unsaturated glycerides and neuroprotective substances like piperine, pantothenic acid, and betaine increased. This once again confirms the close connection between genes and diet.
The results of the research show that the combined analysis of data on genetics, metabolism, and diet will help us predict with much greater accuracy who will develop dementia years before symptoms appear.
Source: Nature medicine
