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March 13, 2020

Alzheimer’s and the future of single-cell NGS

By GE Healthcare Life Sciences

Find out why the latest advances in single-cell next-generation sequencing (NGS), have given patients and their families more hope for the future.


The first signs of dementia

As anyone who has dealt with Alzheimer’s disease is well aware, Alzheimer’s is a progressive disease of the brain. The disease is individual in its manifestation, but the broad outlines of the progression are the same.

First, there may be mild memory loss or moments of confusion, which gradually progress to forgetting the names of friends and family and losing every-day skills. Finally, severe impairment of brain functions renders the Alzheimer’s patient immobile and unable to communicate. The disease has a profound effect not only on the patient, but also on the family and all of those who love and care for them.

On average, people with Alzheimer’s live for eight to ten years after the first symptoms appear, with some living 20 years or more. There are treatments, which can alleviate some of the symptoms or temporarily slow progression, but there is no cure. With increasingly aging populations, researchers are racing to develop a deeper understanding of Alzheimer’s that can lead to better treatments, and possibly a cure.

Single-cell NGS: a ray of hope

A recent article in Nature, a top scientific journal, discusses a promising line of research. The article describes the use of single-cell transcriptomics through next-generation sequencing (NGS) to analyze cells within the brains of people at different stages of Alzheimer’s disease 1.

Find out more about single-cell NGS

What is single-cell transcriptomics?

Transcriptomics is the study of all RNA molecules in a cell. This RNA is produced by the process of transcription from DNA, and encodes the information required to produce protein in cells.

Single-cell transcriptomics uses single-cell RNA sequencing (scRNA-seq), a type of single-cell NGS, to sequence the transcribed RNA within thousands of individual cells. The RNA provides a map to the cellular DNA, which can be explored to reveal mutations that may lead to Alzheimer’s disease.

scRNA-seq works by first isolating individual cells, for instance by fluorescence activated cell sorting (FACS), before capturing the RNA and reverse transcribing it to DNA, ready for amplification and sequencing.

How can single-cell NGS help tackle Alzheimer’s?

The Nature article, titled ‘Single-cell transcriptomic analysis of Alzheimer’s disease’, used single-cell transcriptomics to sequence the RNA from 80 660 single brain cell nuclei across 48 individuals.

The sequencing data provided a unique individual cellular-level view of the transcriptional changes that occur in the brains of people with Alzheimer’s.

As the brain is made up of an array of cell types, being able to look at the cellular level is especially important when trying to tackle a disease as complex as Alzheimer’s. Next-generation sequencing provides the high-throughput sequencing capacity required for research at this level.

Previous tissue-level analyses, such as microarrays or RNA-seq, might have missed the complex changes that occur across different cells and within different cell groups. Within these molecular changes could lie new biomarkers to both help detect the disease earlier, and design and target potential new treatments.

Alzheimer’s disease research: the race is on

What gives hope to many in the Alzheimer’s community—patients, families, researchers, clinicians and care-givers—is that the data from the study was made publicly available. This means that the data can now be used by researchers around the world to map the complex molecular changes that occur across multiple cell types during Alzheimer’s.

Diseases like Alzheimer’s and cancers tend to be treated based on the tissue or organ they affect. But tissues, by definition, are made up of multiple cell types, and organs, of multiple tissues.

Scientists have now realized that even a single tumor can be made up of many sub-populations of cells, each with their own mutational profile, but which together have a large bearing on how the disease develops and responds to treatment.

Single-cell NGS can change the way researchers look at complex diseases, offering a level of insight that wasn’t possible in the past.

It is a race against time between researchers trying to find the key mutations, within a single-cell or population of cells, that trigger the condition and the ongoing progression of the disease for the patient.

We support researchers at each stage of their NGS workflow with DNA amplification, size selection, and PCR clean-up kits. For more specific support with any aspect of your NGS workflow, please contact our Life Sciences support team.

Find out more about how we support molecular diagnostics and custom genomics research

References

  1. Mathys, H. et al. Single-cell transcriptomic analysis of Alzheimer’s disease. Nature 570, 322-351 (2019).

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