Not Just APOE4: Scientists Identify 44 Genes That May Alter Alzheimer’s Risk

An international team of researchers has identified 44 genes that may be involved in the mechanisms underlying Alzheimer’s disease and could become potential targets for future personalized approaches to prevention and treatment. The findings were published in the journal Alzheimer’s & Dementia.

The researchers paid particular attention to the APOE4 variant of the APOE gene. It is considered one of the strongest genetic risk factors for Alzheimer’s disease: people carrying one or two copies of APOE4 may have a four- to 12-fold higher risk of developing the disease than those without the variant. However, carrying APOE4 does not mean that a person will inevitably develop Alzheimer’s.

Scientists from Washington University School of Medicine in St. Louis set out to understand why some APOE4 carriers remain healthy. They analyzed genetic data from nearly 450,000 people of European, African and Japanese ancestry.

The analysis identified 44 genes associated with specific cell types that may play a role in Alzheimer’s disease. For some of these genes, the researchers also identified potential drug compounds that could target the biological mechanisms linked to them.

One particularly notable finding was the association between APOE4-related genes and oligodendrocytes — cells in the nervous system responsible for producing myelin. This protective layer surrounds nerve fibers and enables them to transmit signals efficiently.

According to the researchers, impaired oligodendrocyte function and disrupted myelination may be one of the mechanisms connecting APOE4 with Alzheimer’s disease. Targeting the relevant genes could therefore potentially help preserve the myelin sheath around neurons and reduce the impact of the disease in APOE4 carriers.

The researchers view the findings as a step toward personalized Alzheimer’s treatment, in which doctors could identify the specific biological mechanisms contributing to an individual patient’s disease risk and tailor prevention or treatment strategies according to their genetic profile.

However, the findings do not yet represent a new treatment or establish that targeting these genes can prevent Alzheimer’s disease. Further research will be needed to determine whether the identified genetic pathways can be safely and effectively used for personalized therapies.

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