Biomarkers, either chemical or genetic, are the cornerstone of research to better understand Alzheimer’s disease. The presence of particular biomarkers known to be associated with the disease can potentially serve as risk indicators or confirm early onset for patients who are presenting symptoms. But much more research needs to be done to elucidate the root cause of the disease so that more effective therapies can be developed in the future. 

"Linking together the research element to routine tests is an area known as translational research; a field which is rapidly expanding."

“Our customers play a key role in investigating the genetic causes of this disease,” says Karen Jones, Regional Market Development Senior Manager, EMEA Sequencing, Thermo Fisher Scientific. “We help support their work by serving as their technology partner. Our sequencing solutions are designed to help them better understand the genetic pathways involved for the future development of new treatments.” 


Achieving Efficiency with Gene Panels 


Genetic research sometimes involves whole exome and whole genome sequencing to find those predisposing biomarkers, which might be single-point mutations or small DNA changes. However the time-consuming process of analysing the approximate 19,000 protein-coding genes, which represent less than 1.5% of the human genome is taxing on resources. Expanding the search for disease-causing genetic mutations to the entire genome, including sequences for which no known function has been determined, is an even greater informatics challenge. 

Targeted next-generation sequencing (NGS) technology developed by Thermo Fisher Scientific helps overcome these hurdles. 

While Alzheimer’s might be hereditary, it is also a disease that is affected by lifestyle factors. 

By leveraging gene panels, which contain all the known biomarkers associated with Alzheimer’s disease, researchers are able to very quickly analyse samples and identify these mutations. With a single sequencing run lasting less than 24 hours, for example, researchers are able to screen multiple familial samples across the most likely genes, and determine whether the culprit genes have been inherited and potentially causing the disease. If causative links are found, scientists then use a range of approaches to understand how these gene variants influence disease processes. 

This targeted NGS approach is highly efficient and leverages the most up to date discoveries that have been made in this field of disease research. It enables scientists to better understand why and how the gene variants are involved in the disease process.


Expanding the search for quicker results


Should scientists wish to expand their search beyond known genes, microarray technology allows researchers to spot lots of areas of the human genome on a chip and see whether those are coming up in the samples, and this technology can deliver easy to interpret answers within a few days. Essentially, researchers look for known mutations that have already been identified as potentially causative and see whether they come up. This approach can be used for both genetic variant discovery and gene expression changes. 

‘It’s a way of cutting through the complexity of the human genome to quickly identify genetic factors that correlate with disease onset and progression”, explains Karen. These discoveries lead to the next phase of research which is to develop routine tests that can be used to predict disease predisposition and prognosis as well as to identify future targets for therapy development. Linking together the research element to routine tests is an area known as translational research; a field which is rapidly expanding, thanks to next generation sequencing approaches like these. 


Genetics vs Lifestyle


While Alzheimer’s might be hereditary, it is also a disease that is affected by lifestyle factors. 

Correlating genetic learnings with lifestyle factors offers scientists a way to identify lifestyle changes that can be made to alter disease outcomes. This multifaceted approach is shaping the way that research is developing. 

Research is continually moving forward in this space. Blood-based NGS tests are among the latest approaches coming online as potential tools that one day make their way into routine clinical care. Dr Lesley Cheng, is a post-doctoral scholar at La Trobe University in Melbourne, Australia who works on the development of a novel blood test for detecting Alzheimer’s disease as soon as amyloid plaques first appear in the brain. Her technique involves the identification of microRNA biomarkers within circulating exosomes in our blood, again using Thermo Fisher’s next generation sequencing technology. She is turning these discoveries into fast and cost-effective tests using Applied BiosystemsTM TaqMan® assays. 


To read more about approaches for studying genetic diseases like Alzheimer’s click here.