Spanish researchers identify one of the most influential risk factors for Alzheimer’s disease

MURcia (EP). Researchers National Center for Cardiovascular Research (CNIC) determined that one of the genes considered to be the most influential risk factor in the development of late-onset Alzheimer’s disease, the apolipoprotein E4 (APOE4) gene, is also associated with an increased risk of developing subclinical atherosclerosis in midlife. .

The study also shows that, conversely, people carrying the APOE2 variant are protected; This option is also considered protective against the development of Alzheimer’s disease. In addition, the results of this study, published in the journal Circulation Research, shed light on the role of APOE in the development of cardiovascular diseases and have important therapeutic and preventive implications for cardiovascular health, especially in the first half of the 2000s. adulthood.

The APOE gene is known to encode apolipoprotein E, which, among other important functions, helps transport lipids in the blood. The gene has three main alleles that give rise to different isoforms of this lipoprotein: APOE2, APOE3 and APOE4.

“Inheriting one or another of these alleles gives a person a different risk of developing various diseases, including cardiovascular disease and Alzheimer’s disease,” explain Cortés Canteli, a neuroscientist at the CNIC, and researcher Miguel Serveta at the Health Research Institute of the Jiménez Díaz Foundation. who coordinated the study with Dr. Valentin Fuster, Director General of the CNIC.

People who inherit APOE4 have high cholesterol levels and therefore a higher risk of developing atherosclerosis, while people with APOE2 have lower cholesterol levels and a lower prevalence of atherosclerosis.

However, the mechanisms responsible for these associations are complex, and the influence of age, sex and other cardiovascular risk factors remains unclear, especially in the early stages of disease development.

The CNIC research team has now confirmed that middle-aged people from the PESA-CNIC-Santander study (40 to 54 years old) have a greater risk of developing subclinical atherosclerosis in people with APOE4 because they have a higher risk of developing subclinical atherosclerosis. elevated levels of LDL cholesterol (or “bad” cholesterol), which opens the door to early intervention strategies.

Additionally, the study shows that people with APOE2 are less likely to suffer from subclinical atherosclerosis of the carotid, femoral, and coronary arteries. The researchers explain that this protection against atherosclerosis is due to normal triglyceride levels or, in the case of women and the younger group (40 to 44 years old), cholesterol-lowering LDL levels.

“This all re-emphasizes the importance of maintaining a healthy lifestyle,” says Fuster, also president of the Cardiovascular Institute and “chief physician” at Mount Sinai Medical Center in New York City.

However, in men and older adults (aged 45 to 54 years), this APOE2 protection appears to require some additional mechanism. In fact, the researchers found an enrichment of molecular pathways associated with anti-inflammatory processes and a decrease in genes involved in blood clotting and complement activation in APOE2 carriers.

This suggests, says Dr. Raquel Toribio Fernandez, co-author of the study, that “the modulation of the immune system present in people with APOE2 may contribute to protection against atherosclerosis in the earliest stages.”

These results suggest that knowing which APOE isoform is present in each person may improve cardiovascular risk stratification, “especially in the early stages of cardiovascular disease,” emphasizes Dr. Catarina Tristan Pereira, one of the paper’s original signatories.

PESA-CNIC-Santander, led by Fuster, is a prospective study of more than 4,000 asymptomatic middle-aged participants who have been carefully assessed since 2010 for the presence and development of subclinical atherosclerosis.