In the field of medical research, a recent study conducted by the Sant Pau Research Institute in Barcelona has brought to light a new genetic form of Alzheimer’s disease. This discovery, published in the journal ‘Nature Medicine’, was led by Juan Fortea, head of the Memory Unit of the Neurology Service. The research has highlighted that individuals over the age of 65, carriers of two copies of the ApoE4 gene, present biological markers typical of Alzheimer’s in brain or in the cerebrospinal fluid, as well as testing positive on PET scans.
The ApoE4 gene has been known for over three decades and associated with a high risk of developing Alzheimer’s. However, research has shown that the presence of two copies of this gene not only increases the risk but constitutes a distinct shape of this neurodegenerative disease. This aspect is crucial since individuals with a double copy of the ApoE4 gene, who represent approximately 2-3% of the population, show signs of the disease much earlier than those who possess other variants of the gene.
The analysis included data from 3,297 brain donors, with 273 individuals homozygous for ApoE4, from the National Alzheimer’s Coordinating Center in the United States. Additionally, we examined clinical data and biomarkers from more than 10,000 people with indicators of Alzheimer’s, including 519 homozygotes for ApoE4. The results revealed that almost all homozygotes for ApoE4 manifested Alzheimer’s disease and had significantly higher levels of biomarkers associated with the disease already at age 55, compared to those with the ApoE3 variant. By age 65, more than 95% of ApoE4 homozygotes had abnormal levels of amyloid protein in their cerebrospinal fluid, an early indicator of Alzheimer’s, and 75% had PET scans positive for amyloid.
These data not only confirm that the ApoE4 genetic variant is a risk factor for Alzheimer’s, but suggest that it constitutes a specific genetic form of the disease. This distinction is fundamental to the development of personalized prevention strategiesclinical trials and therapeutic approaches aimed at this particular population.
