Tackling Alzheimer’s: Purdue scientists map genetic risks for women

02-19-2025

Alzheimer’s disease is one of the most devastating neurological disorders, affecting millions of people worldwide.

Despite decades of research, understanding the precise biological mechanisms behind the disease has remained a challenge. Now, an interdisciplinary team of researchers at Purdue University, led by Professor of Biological Sciences, Peristera Paschou, has made significant strides in uncovering genetic and biological factors that contribute to Alzheimer’s—particularly in women. Their work, published in Acta Neuropathologica Communications, provides new insights that could pave the way for more personalized treatment approaches.

Bridging Biology, Computer Science, and Medicinal Chemistry

This research is the result of collaboration across multiple disciplines at Purdue. In addition to Paschou, key contributors include Professor Petros Drineas from the Department of Computer Science and Professor Chris Rochet from the Department of Medicinal Chemistry and Molecular Pharmacology. Graduate students Yin Jin, Apostolia Topaloudi, Sudhanshu Shekhar, Guangxin Chen, Alicia Nicole Scott, and Bryce David Colon also played essential roles in the project.

The team’s approach leveraged advanced computational techniques, large-scale genetic analysis, and expertise in neurobiology to better understand the disease. Their findings were supported by funding from the Purdue Institute for Drug Discovery and National Science Foundation grants awarded to Paschou and Drineas.

A Sex-Specific Look at Alzheimer’s Genetics

A major breakthrough in this study was the discovery that the BIN1 gene plays a particularly significant role in women with Alzheimer’s. Since women are at a higher risk for developing the disease, identifying specific genetic factors that contribute to this disparity is crucial. The research also highlighted the role of QRFPR, a gene associated with regulating circadian rhythms and feeding behaviors, in the progression of Alzheimer’s in women.

By analyzing genetic data from nearly 7,000 individuals across 14 large-scale datasets, the team was able to identify patterns in genetic variations linked to Alzheimer’s-related brain pathology. Their use of Genome-Wide Association Studies (GWAS) and Mendelian Randomization (MR) allowed them to explore how these genetic changes contribute to the disease’s progression.

A Systems-Level View of Alzheimer’s Progression

Beyond genetics, the study uncovered a complex interplay between cholesterol metabolism, inflammation, and liver function in Alzheimer’s disease. The researchers found that high levels of LDL cholesterol—commonly known as “bad cholesterol”—not only increase the risk of Alzheimer’s but also become further disrupted as the disease progresses. This creates a harmful feedback loop where metabolic and immune system dysfunction accelerate brain degeneration.

Paschou compares the disease’s progression to a city-wide traffic system where certain intersections, represented by genetic and biological pathways, begin to fail. These failures lead to widespread congestion—akin to the brain’s deteriorating ability to function properly. By mapping out these failures, the research provides a clearer blueprint for identifying intervention points that could prevent further damage.

A Foundation for Future Treatments

The implications of this research extend beyond academia. By identifying specific genetic and biological markers of Alzheimer’s, the findings could help guide the development of targeted therapies, particularly those tailored for women. Additionally, the study emphasizes the importance of systemic health factors, such as cholesterol and inflammation, in managing and potentially slowing the progression of the disease.

“Our work underscores the necessity of an interdisciplinary approach in tackling complex diseases like Alzheimer’s,” said Paschou. “By bringing together expertise from biological sciences, computer science, and pharmacology, we are able to generate insights that would not be possible within a single field.”

Advancing Research at Purdue

The study was conducted under the umbrella of the Purdue Institute for Integrative Neuroscience, which fosters collaboration among scientists from diverse disciplines. This research also benefited from Purdue’s commitment to high-impact studies that address pressing global health challenges.

With continued support and interdisciplinary collaboration, the team hopes their findings will contribute to the development of novel diagnostic tools and treatments. Their research not only enhances our understanding of Alzheimer’s but also sets the stage for future studies that could improve patient outcomes.

As scientists work to unravel the complexities of Alzheimer’s, Purdue’s researchers remain at the forefront, using cutting-edge techniques to bring us closer to solutions. Their findings remind us that solving medical mysteries often requires looking beyond traditional boundaries and embracing the power of collaboration.

 

About the Department of Biological Sciences at Purdue University

Purdue Biological Sciences is the largest department in the Life Sciences at Purdue University. As part of Purdue One Health, we are dedicated to pioneering scientific discoveries and transformative education at the cutting edge of innovation. From molecules to cells, from tissues to organisms, from populations to ecosystems - we bring together multiple perspectives, integrating across biological scales to advance our understanding of life and tackle the world’s most pressing challenges. Learn more at bio.purdue.edu/.

 

 

Writer: Alisha Referda, areferda@purdue.edu

Source: Peristera Paschou, ppaschou@purdue.edu