A team of scientists appears to have discovered a previously hidden genetic cause of Alzheimer’s. In a new study Monday, researchers found strong evidence that people who carry two copies of a genetic variation already linked to Alzheimer’s risk are virtually destined to develop the neurodegenerative disease as they age. Up to 2% of the general population could have the same mutation, suggesting that the genetic risk of Alzheimer’s is greater than currently thought.
Alzheimer’s is the most common form of dementia, currently affected around 7 million Americans. It is a complex disease that can have many causes various risk factors Age, cardiovascular diseases and genetics are behind this. Rare mutations are known to almost always cause someone to develop Alzheimer’s at a much younger age than usual, while other mutations appear to increase the risk of the classic form of Alzheimer’s, which typically occurs after age 65. One of these latter mutations affects the apolipoprotein E gene, or APOEand is known as APOE4.
About a quarter of the population carries at least one copy APOE4, and the variant is often studied by scientists as an important aspect of Alzheimer’s risk. Often these studies do not distinguish between people who have one or both copies of the gene, but some research has shown that these are double carriers, also known as APOE4 Homozygotes have a much higher risk of developing Alzheimer’s than others.
A large team of researchers from Spain and the USA tried to clarify the question. To do this, they analyzed brain donor data from the National Alzheimer’s Coordinating Center (NACC), as well as data from five other large-scale studies tracking people’s biomarkers associated with Alzheimer’s, including hers APOE4 Status. In total, the analysis included over 13,000 people.
In the NACC data, researchers found that almost everyone has two APOE4 Genes showed moderate to high levels of brain changes linked to Alzheimer’s disease at the time of her death. For comparison: the same only applied to 50% of those with APOE3the most common APOE variant, and is not thought to affect Alzheimer’s risk. In the biomarker data, the team also found that almost everyone had two APOE4 The copies had abnormal levels of amyloid beta in the spinal fluid (a possible early sign of the disease) at age 65, while 75% had positive amyloid scans. By age 80, nearly 90% of these carriers had all the biomarkers associated with amyloid and tau (another key Alzheimer’s protein) that the researchers could track.
Not everyone with these changes shows clinical symptoms of Alzheimer’s before death. But the findings published Monday in the journal Nature Medicine provide a clear example of near-total penetrance, the authors say – the likelihood that a genetic mutation causes a particular trait. In this case the one with two APOE4 Genes seem almost certain to develop at least the early signs of Alzheimer’s by the time they reach their mid-60s. Given this certainty, it is more accurate to classify this mutation as a specific “genetic form” of Alzheimer’s, the researchers argue. They also note that an estimated 2% of the population has two of them APOE4 copies, which would make this form of Alzheimer’s one of the most common diseases linked to a single gene.
The findings, if confirmed by other researchers, could lead to important changes in the way we study Alzheimer’s. First of all, it should lead to a more comprehensive definition of genetic Alzheimer’s disease APOE4 Form known to cause Alzheimer’s disease, usually at an older age than other genetic causes. Given the much higher danger involved with two APOE4 The researchers say that future studies should not bundle copies with individual copy media. And just knowing this increased risk should hopefully help scientists better understand how Alzheimer’s occurs, which could one day lead to more effective treatments for it.
“In summary, our study provides compelling evidence for this APOE4 Homozygotes [i.e. two APOE4 alleles, or copies] represent a unique, genetically determined form [Alzheimer’s disease]which has important implications for public health, genetic counseling of carriers, and future research directions,” they wrote.