A new genetic form of Alzheimer’s has been discovered by Spanish researchers of 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 characteristics of Alzheimer’s in the brain or biomarkers of disease in cerebrospinal fluid and PET scans. The work also indicates that ApoE4 homozygous individuals develop Alzheimer’s disease earlier than people with other ApoE4 gene variants.
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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 has been known for over 30 years – he recalls – and is known to be associated with a higher risk of getting 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 “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 markers of Alzheimer’s, including 519 ApoE4 homozygotes.
“The results – the scientists report – indicate that virtually all ApoE4 homozygotes exhibited Alzheimer’s disease and had higher levels of biomarkers associated with the disease at age 55, 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 in Alzheimer’s disease – and 75% had amyloid-positive PET scans.”
Based on these observations, the authors indicate that “the ApoE4 genetic variant is not only a risk factor for Alzheimer’s disease, as previously thought, but may represent a distinct 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 specific 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 who today studies the molecular structure of the ApoE gene at the Center of supercomputing in Barcelona.
