Spanish Researchers Discover New Genetic Form of Alzheimer’s Linked to ApoE4 Gene

A Spanish researchers have discovered a new genetic form of Alzheimer’s of the Sant Pau Research Institute in Barcelona, ​​​​​​​​​​​​​​​​​authors of a study published in ‘Nature Medicine’. Scientists from the field of Neurological Disease Research, Neuroscience and Mental Health of the Institute, led by Juan Fortea, director of the Neurology Service Memory Unit of the same structure, noticed that more than 95% of people over 65 with two copies of the ApoE4 gene (ApoE4 homozygotes) show the biological features of Alzheimer’s in the brain or disease biomarkers in cerebrospinal fluid and PET scans. The work also shows that homozygous ApoE4 people develop Alzheimer’s disease earlier than people with other variants of the ApoE4 gene.

I study

The results suggest “two copies of the ApoE4 gene may represent a new genetic form of primary dementia, explains Fortea. “The ApoE4 gene has been known for more than 30 years – he recalls – and it is known that it is associated with a higher risk of getting Alzheimer’s disease. But now we know that almost everyone with two copies of this gene develops Alzheimer’s biology”. Having understood this “it is important – confirms the expert – because” homozygous ApoE4s “represent 2-3% of the population”.

The researchers evaluated clinical, pathological, and biomarker changes in ApoE4 homozygous subjects to determine their Alzheimer’s risk. They used data from 3,297 brain donors, including samples from 273 homozygotes for ApoE4, from the US National Alzheimer’s Coordinating Center. They also used clinical and biomarker information from more than 10,000 people with Alzheimer’s symptoms, including 519 ApoE4 homozygotes.

“The results – the scientists report – indicate that almost all ApoE4 homozygotes showed Alzheimer’s disease and that there were higher levels of biomarkers associated with the disease at age 55, the compared to people with the ApoE3 variant. At age 65, more than 95% of ApoE4 homozygotes had abnormal levels of amyloid protein in the cerebrospinal fluid—a key early pathological feature of Alzheimer’s disease—and 75% had positive amyloid PET scans.

Based on these observations, the authors suggest that “the ApoE4 genetic variant is not only a risk factor for Alzheimer’s disease, as previously thought, but may represent a specific genetic form of the disease .”

According to the researchers, “these findings could be useful for the development of personalized prevention strategies, clinical trials and targeted therapeutic approaches for this special population” with two copies of the ApoE4 gene. “The data highlight the importance of monitoring homozygotes for ApoE4 from an early age for preventive interventions”, says Víctor Montal who participated in the study when he worked at the Sant Pau Research Institute and is currently studying the molecular structure of the ApoE gene at the Supercomputing Center in Barcelona.