Gene of the Month – July: APOE

APOE is not only a well-known risk gene for Alzheimer’s disease, but primarily an important regulator of the immune system—according to a study published in Nature Medicine. Apolipoprotein E (ApoE) plays a central role in the body’s lipid metabolism and is essential for transporting fatty acids, cholesterol, and other lipids to nerve cells. It has been known that a specific variant, APOE4, is the strongest genetic risk factor for late-onset Alzheimer’s disease. Now, researchers have discovered that APOE4 may also cause an increased vulnerability to other neurodegenerative diseases, such as frontotemporal dementia, Parkinson’s disease, or amyotrophic lateral sclerosis (ALS).

In the large-scale study, the authors used machine learning to analyze more than 10,000 blood, brain, and cerebrospinal fluid samples from individuals both with and without neurodegenerative diseases. They found that people carrying the APOE4 variant share a consistent pattern of proteins, primarily related to the immune system and inflammatory processes. This protein signature was present in all samples, regardless of the disease diagnosed or whether the individual showed symptoms.

However, the scientists also observed that while APOE4 increases the biological vulnerability to a neurodegenerative disease, other factors—such as high blood pressure or smoking—can interact with this genetic susceptibility, depending on the specific disease. These results could form the basis for the development of precise biomarkers and tailored prevention strategies against various neurodegenerative diseases.

Shvetcov A, Thomson S, Cho AN, … Finney CA. Proteome profiling of cerebrospinal fluid using machine learning shows a unique protein signature associated with APOE4 genotype. Aging Cell. 2025 Apr;24(4):e14439. doi: 10.1111/acel.14439.

Article in PubMed

Gene of the Month – July: APOE

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