In a groundbreaking study, researchers have identified a genetic form of late-in-life Alzheimer's disease, specifically found in individuals who inherit two copies of the APOE4 gene. While it has been well-established that the APOE4 gene is a risk factor for Alzheimer's, this new research suggests that having two copies of this gene, rather than just one, can be an underlying cause of the debilitating condition.

Led by Dr. Juan Fortea of the Sant Pau Research Institute in Barcelona, Spain, the study has uncovered significant findings that have profound implications. One of the key revelations is that individuals carrying two copies of APOE4 may experience symptoms seven to ten years earlier than other older adults who develop Alzheimer's.

It is estimated that approximately 15% of Alzheimer's patients carry two copies of the APOE4 gene, indicating that the cause of these cases can be directly attributed to inherited genetic factors. Until now, genetic forms of Alzheimer's were believed to only affect individuals at much younger ages, accounting for less than 1% of overall cases.

The implications of this research are significant, highlighting the urgent need to develop targeted treatments that specifically address the APOE4 gene. However, due to the increased susceptibility of individuals with this gene pair to dangerous side effects, caution must be exercised when prescribing the only known drug that has shown modest success in slowing the progression of the disease, called Leqembi.

Dr. Reisa Sperling, a coauthor of the study from Harvard-affiliated Brigham and Women's Hospital in Boston, emphasizes the importance of focusing on this high-risk group before they develop symptoms. Sperling is dedicated to finding ways to prevent or delay the onset of Alzheimer's, emphasizing that this revelation serves as a crucial opportunity for intervention.

Despite these significant findings, it is important not to panic or rush for gene testing, as this particular gene combination only contributes to a minority of Alzheimer's cases. According to Sperling, it is crucial to consider a family history of the disease when evaluating the need for genetic testing.

With over 6 million Americans and millions more worldwide affected by Alzheimer's, the identification of this genetic form opens doors for further research and understanding. While certain genes have been associated with early-onset forms of Alzheimer's, the APOE4 gene has long been recognized as the most significant genetic risk factor for late-in-life Alzheimer's, with two copies of the gene increasing the risk further. It is estimated that approximately 2% of the global population carries two inherited copies of the APOE4 gene.

By analyzing brain samples from 3,297 donors and studying data from over 10,000 individuals participating in Alzheimer's studies, Dr. Fortea's team discovered that those with two copies of APOE4 showed increased accumulation of amyloid plaque, a hallmark of Alzheimer's, even as early as age 55. Additionally, brain scans revealed significant plaque buildup in nearly three-quarters of these double carriers by age 65, aligning with the earlier onset of symptoms in this group.

Dr. Eliezer Masliah of the National Institute on Aging notes the remarkable similarity between the underlying biology of this genetic form and early-onset inherited types of Alzheimer's. These findings warrant the development of targeted therapies and potential gene therapies that specifically address the APOE4 gene.

Further research is needed to understand why not all individuals with two APOE4 genes develop Alzheimer's symptoms. In-depth investigations are also required to determine the effectiveness and safety of drugs like Leqembi in this high-risk population.

It is crucial to broaden research to diverse populations, as existing studies have primarily focused on individuals of European ancestry. The effects of the APOE4 gene need to be examined comprehensively across various ethnic backgrounds.

While gene tests are currently limited to assessing the eligibility of individuals for Leqembi or for enrollment in Alzheimer's research studies, it is clear that the identification of this specific gene combination offers valuable insights for potential preventive strategies.

As the battle against Alzheimer's disease continues, this groundbreaking study has shed light on the genetic factors contributing to its development and progression. With a deeper understanding of the role played by the APOE4 gene, scientists and medical professionals are one step closer to developing effective treatments and interventions for this devastating disease.