Alzheimer’s disease, genetic form responsible for 15-20% of cases discovered

A new genetic form of Alzheimer’s linked to a variant of the Apoe gene has been discovered. Scientists from the Sant Pau Research Institute in Barcelona, ​​led by Juan Fortea, director of the Memory Unit of the Neurology Service, observed that over 95% of over 65s have 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 ApoE4 homozygous individuals develop Alzheimer’s disease earlier than people with other variants of the ApoE4 gene.

The results suggest that “having two copies of the ApoE4 gene might represent a new genetic form” of the main form of dementia, explains Fortea. «The ApoE4 gene has been known for over 30 years – you remember – and is known to be associated with a higher risk of getting Alzheimer’s disease. But we now know that virtually 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”. This discovery, published in the journal Nature Medicine, it might lead to changes in disease diagnosis and management and influence how clinical trials are designed.

Also in Nature, the team said the predictability of the age at which symptoms began was similar to other genetic forms of the disease such as autosomal dominant Alzheimer’s disease (ADAD) and Alzheimer’s disease in Down syndrome (DSAD). .
Dr. Victor Montal, co-author from the Barcelona Supercomputing Center, said the research catalyzed a paradigm shift in understanding the disease. «Whereas previously, the etiology of dementia was known in less than 1% of cases, our work has now allowed identification of causal factors in 15%-20% of cases».

However, the study did not shed light on the risk of developing dementia in people with two copies of ApoE4. Researchers reported how autopsy results on 3,297 brain donors revealed that nearly all of the 273 donors with two copies of ApoE4 showed signs of Alzheimer’s in the brain. Furthermore, they also analyzed clinical data from more than 10,000 people, revealing that by age 65, nearly all of the 519 people with two copies of ApoE4 had abnormal levels of beta-amyloid, the protein implicated in Alzheimer’s, in their cerebrospinal fluid and 75% had positive amyloid scans. The prevalence of biomarkers for the disease also increased with age.

As for the age of onset of symptoms, the team found that it was regarding 7-10 years earlier in people with two copies of ApoE4, around 65 years old, compared to those without the variant.