2024-01-30 09:15:37
In a new study, it has been determined that one of the genes considered to be the strongest risk factor for developing late-onset Alzheimer’s disease, the apolipoprotein E4 (APOE4) gene, is also associated with an increased risk of developing Subclinical atherosclerosis in middle age. The research also shows that, on the contrary, people carrying the APOE2 variant are protected; This variant is also considered protective for the development of Alzheimer’s.
The study is the work of researchers from the National Center for Cardiovascular Research (CNIC), a center dependent on the Carlos III Health Institute (ISCIII), an organization attached to the Ministry of Science, Innovation and Universities, in Spain.
The results of this study, which has been coordinated by Dr. Marta Cortés Canteli and Dr. Valentín Fuster, General Director of the CNIC, provide new and revealing data on the role of APOE in the development of cardiovascular diseases, and have important therapeutic implications. and preventive for cardiovascular health, especially in the first half of adult life.
It is known that the APOE gene codes for 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. “Having inherited one or another of these alleles gives the individual a different risk of developing different diseases, including cardiovascular disease and Alzheimer’s disease,” explains Dr. Cortés Canteli, neuroscientist at the CNIC and Miguel Servet researcher at the Health Research Institute. Jiménez Díaz Foundation.
People who inherit APOE4 have high cholesterol levels and a consequently higher risk of suffering from atherosclerosis, while those who have APOE2 have lower cholesterol and a lower prevalence of atherosclerosis.
However, the mechanisms responsible for these associations are complex and the impact of age, sex, and other cardiovascular risk factors was unclear, particularly in the early stages of disease development.
Members of the research team. From left to right: Catarina Tristan Pereira, Enrique Lara Pezzi, Rachel Toribio Fernandez, Borja Ibanez, Valentin Fuster, Sergio Callejas, Marta Cortes Canteli, Ana Dopazo, Pilar Martin, Ines Garcia Lunar and Irene Fernandez Nueda. (Photo: CNIC)
What the CNIC team of researchers has now done is to corroborate in middle-aged individuals from the PESA-CNIC-Santander study (between 40 and 54 years old) that there is a greater risk of developing subclinical atherosclerosis in APOE4 individuals because they have higher elevated LDL cholesterol (or “bad” cholesterol), which opens a window to implement early intervention strategies. (PESA-CNIC-Santander, directed by Dr. Fuster, is a prospective study that includes more than 4,000 asymptomatic middle-aged participants in whom the presence and development of subclinical atherosclerosis has been exhaustively evaluated since 2010).
In addition, the new research reveals that people with APOE2 had less subclinical atherosclerosis in the carotid, femoral and coronary arteries.
The researchers explain that this protection against atherosclerosis is due to having normal levels of triglycerides, or, in the case of women and in the younger group (40 to 44 years of age), to having levels of LDL- lower cholesterol. “All of this highlights, once again, the importance of maintaining a healthy lifestyle,” says Dr. Fuster, also President of the Cardiovascular Institute and “Physician-in-Chief” at Mount Sinai Medical Center in New York.
However, in men and older people (ages 45 to 54), such APOE2 protection seemed to require some additional mechanism. In fact, the researchers identified an enrichment in molecular pathways associated with anti-inflammatory processes and a decrease in genes involved in coagulation processes and complement activation in APOE2 carriers. This suggests, says Dr. Raquel Toribio Fernández, co-author of the study, “that the modulation of the immune system present in APOE2 individuals could be contributing to protection against atherosclerosis in the earliest stages.”
These results suggest that knowing which APOE isoform is present in each individual could improve cardiovascular risk stratification, “especially during the initial stages of cardiovascular disease development,” highlights Dr. Catarina Tristão Pereira, co-author of the study.
The study is titled “Apolipoprotein E-ε2 and resistance to atherosclerosis in midlife: the PESA observational study.” And it has been published in the academic journal Circulation Research. (Source: CNIC)
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