Researchers have revealed a pioneering ranking showcasing the importance of every gene and protein linked to Alzheimer’s Disease development.
Researchers at The Jackson Laboratory have unveiled a groundbreaking ranking highlighting the role and significance of each gene and protein associated with Alzheimer’s Disease ahead of the Alzheimer’s Association International Conference on July 28.
By delving into the human genome, scrutinizing protein encoding processes, and tracking RNA expression, researchers are gaining a deeper insight into the intricate genetic and cellular mechanisms behind dementia. However, the multitude of research paths unveiled by new technologies presents a challenge: predicting which avenues will yield effective treatments remains uncertain.
“We have numerous potential targets, yet identifying the most viable ones remains a puzzle,” explained Greg Carter, the Bernard and Lusia Milch Endowed Chair at the Jackson Laboratory (JAX) and lead researcher of the study. “Given the slow and expensive nature of drug development, an effective method to prioritize these insights is essential.”
Now, Carter and his team at JAX, in partnership with experts from Stanford University School of Medicine, Emory University, and Sage Bionetworks, are addressing this challenge by offering the first comprehensive ranking of each gene and protein’s role in Alzheimer’s disease development. Their findings are outlined in the July edition of Alzheimer’s & Dementia in anticipation of the Alzheimer’s Association International Conference on July 28.
“This study represents the most extensive analysis to date of Alzheimer’s patients’ brains,” Carter highlighted. “It merges research across fields such as genetics and -omics, covering the patient’s lifespan, at a scope previously unattainable.”
Employing machine learning techniques, the team amalgamated insights from over twenty large genetic studies and multi-omic examinations of nearly 2,900 brains to pinpoint numerous potential targets for therapeutic interventions. These targets were then categorized into 19 distinct “biodomains” representing the biological mechanisms that contribute to Alzheimer’s disease.
Instead of generating an undifferentiated list of genes and proteins, Carter and his team associated each target with a specific therapeutic hypothesis, simplifying comprehension of their functions and facilitating the identification of candidates for experimental validation.
The researchers also flagged targets likely relevant in the early stages of Alzheimer’s, supporting the creation of new diagnostic and therapeutic tools for pre-symptomatic interventions. Carter elucidated, “This is immensely important yet challenging: most data are derived from post-mortem brains, akin to deducing the origin of a forest fire after complete incineration. Our computer modeling effectively traces the disease’s progression backward to identify early markers corresponding to late-stage pathology.”
This method has already led to significant revelations, such as uncovering evidence suggesting a substantial role of mitochondria – the cell’s powerhouse – in the initial stages of Alzheimer’s disease. The team found promising targets within this biodomain, indicating that mitochondrial function could serve as a robust early indicator of Alzheimer’s and a principal contributor to its progression.
The study findings and complete dataset are publicly accessible through the Emory-Sage-Structural Genomics Consortium-JAX TREAT-AD Center, part of an NIH-supported initiative dedicated to mitigating the risks associated with Alzheimer’s research. This resource provides researchers and biotech pioneers with a foundational tool to bolster more targeted and informed future investigations. “We have adopted a highly transparent approach,” expressed Carter. “Any biotech or pharmaceutical company that wishes to capitalize on this data can do so – and we encourage their involvement.”
