Genetic variants involved in Alzheimer's disease are linked to atherosclerosis

Scientists at the National Center for Cardiovascular Research (CNIC) have determined that one of the genes under consideration is the strongest risk factor for the development of late-stage Alzheimer's diseasethe apolipoprotein E4 (APOE4) gene, is also associated with a increased risk of subclinical atherosclerosis middle aged.

Atherosclerosis occurs when fat, cholesterol and other substances build up in the artery walls. It usually doesn't cause symptoms until blood flow to a part of the body is slowed or blocked.

The research, published in the journal Circulation research and coordinated by Marta Cortes Canteli And Valentin Fusteralso shows that, on the contrary, carriers of the APOE2 variant are protected; This variant is also considered to be protective against the development of Alzheimer's disease.

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

“Having inherited one or other of these alleles increases the individual's risk of developing various pathologies, including cardiovascular disease and Alzheimer's disease,” explains Cortés Canteli, neuroscientist at the CNIC and Miguel Servet researcher at the Jiménez Health Research Institute Diaz Foundation.

People who have inherited 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 cardiovascular disease.

However, the mechanisms responsible for these associations are complex and the influence of age, gender and other cardiovascular risk factors has been unclear, particularly in the early stages of disease development.

APOE4 carriers have an increased risk of developing subclinical atherosclerosis in middle age, while APOE2 carriers are protected. / CNIC

Apply early intervention strategies

Now the team has confirmed in middle-aged people (between 40 and 54 years old) that APOE4 people are at higher risk of developing subclinical atherosclerosis because having high levels of LDL cholesterol (the so-called bad cholesterol) opens a window to implement early intervention strategies.

The research, based on data from the PESA-CNIC-Santander study, shows that people with APOE2 had less subclinical atherosclerosis in the carotid, femoral and coronary arteries.

The authors explain that this protection is due to normal triglyceride levels or, in women and in the younger group (40 to 44 years), lower LDL cholesterol levels. “All of this underlines once again how important it is to maintain a healthy lifestyle,” says Fuster, director of the CNIC.

However, in men and older people (45 to 54 years), such APOE2 protection appeared to require an additional mechanism. In fact, the researchers found in APOE2 carriers an enrichment of molecular signaling pathways associated with anti-inflammatory processes and a decrease in genes involved in coagulation processes and complement activation.

“This suggests that modulation of the immune system in APOE2 individuals may contribute to protection against atherosclerosis in the earliest stages,” he says. Raquel Toribio FernandezCo-first author of the study.

Knowing which APOE isoform is present in each individual could improve cardiovascular risk stratification, “particularly in the early stages of cardiovascular disease development,” he concludes. Catarina Tristao PereiraCo-first signatory of the article.