Alzheimer’s, a new genetic form discovered: individuals with two copies of the ApoE4 gene almost certainly develop the disease

Genetics may be the cause and not just a risk factor for some cases of Alzheimer’s. A new genetic form of Alzheimer’s it was in fact discovered by Spanish researchers from the Sant Pau Research Institute in Barcelona, ​​authors of a study published in «Nature Medicine». Scientists from the Institute’s Neurological Diseases, Neuroscience and Mental Health Research area, led by Juan Fortea, director of the Memory Unit of the Neurology Service of the same structure, observed that over 95% of over 65s with two copies of the ApoE4 gene (ApoE4 homozygotes) show biological features of Alzheimer’s in the brain or biomarkers of the pathology in cerebrospinal fluid and PET scans. The work also indicates that gApoE4 homozygous individuals develop Alzheimer’s earlier than people with other variants of the ApoE4 gene.

ApoE4 homozygotes represent 2-3% of the population

The results suggest that «having two copies of the ApoE4 gene could represent a new genetic form» of the main form of
dementia, explains Fortea. “The ApoE4 gene it has been known for over 30 years – he recalls – and it is known to be associated with a higher risk of Alzheimer’s disease. But now we know that practically all individuals with two copies of this gene develop Alzheimer’s biology». Having understood this «is important – underlines the expert – because “homozygous ApoE4s”they represent 2-3% of the population». At least two people out of 100 are carriers of the double copy of the variant and will almost certainly fall ill with Alzheimer’s. According to experts, however, people with only one copy of the ApoE4 variant constitute approximately 15-25% of the general population and approximately 50% of patients suffering from Alzheimer’s dementia. «A single copy of ApoE4 would continue to be considered a risk factor, not sufficient to cause Alzheimer’s» underlined Dr. Fortea

Abnormal levels of amyloid beta protein

The new study analyzed data from more than 500 people with two copies of ApoE4, a significantly larger number than previous studies. Since nearly all of these patients developed biomarkers of Alzheimer’s disease, the authors conclude that two copies of ApoE4 should now be considered a cause of Alzheimer’s, not simply a risk factor.
Research has found that patients have also developed Alzheimer’s pathology relatively young age. By age 55, more than 95% had biological markers associated with the disease. By age 65, almost everyone had abnormal levels of accumulation of the amyloid beta protein in the brain, a hallmark of Alzheimer’s disease. And many began developing symptoms of cognitive decline at age 65, younger than most people without the APOE4 variant.

The development of new therapies

Currently, the vast majority of Alzheimer’s cases do not have a clearly identified cause. If the new classification for this particular small subgroup of patients with double copies of the ApoE4 variant proposed by the new study is confirmed, this subtype of Alzheimer’s would become one of the most common genetic diseases in the world. This could lead to an expansion of efforts for disease treatments, including gene therapy, which consists in providing the body with a correct copy of defective genes, as is already happening for diseases such as haemophilia or SMA, or transforming ApoE4 into another variant called ApoE2, which instead appears to protect the brain from Alzheimer’s. According to the researchers, «these results could be useful for the development of personalized prevention strategiesclinical studies and targeted therapeutic approaches for this specific population” with two copies of the ApoE4 gene. «The data highlight the importance of monitoring ApoE4 homozygotes from an early age preventive interventions», says Víctor Montal who participated in the study when he worked at the Sant Pau Research Institute and who today studies the molecular structure of the ApoE gene at the Supercomputing Center of Barcelona.

The case of Chris Hemsworth

The general public’s attention on genetics and Alzheimer’s was sparked in 2022 when actor Chris Hemsworth revealed his genetic predisposition to Alzheimer’s characterized by two copies of the ApoE4 gene. After that revelation, Hemsworth shifted his focus to healthy living, as discussed in the series Limitless. Studies indicate that diet, exercise, adequate sleep can alter the expression of genes associated with disease risk. And just in these days a new work published in the magazine BMJ Evidence-Based Medicine highlighted how a healthy lifestyle can offset the impact of genetics by over 60% and extend your life by a few years. Experts agree in underlining that even those who are genetically predisposed to a disease can certainly postpone the appointment with the neurodegenerative disease by adopting a healthy lifestyle.