On 8 May, Prof. Simon Lovestone and colleagues reported that the JAK-STAT signalling pathway, which is known to promote inflammatory conditions such as Crohn’s disease and psoriasis, may also be involved in the development of Alzheimer’s disease (AD).
Recent technological advances in next-generation sequencing (NGS) have yielded vast quantities of genetic data, transforming the scientific landscape. Using high-performance computers, researchers can now study genetic data from thousands of people with different health conditions, identifying novel genes that may contribute to the development of disease. The starting point for this study, published in Cells, was to probe a large catalogue of genome sequencing data (the NHGRI-EBI GWAS database) for susceptibility genes shared between people with AD and people with other conditions such as Crohn’s disease, psoriasis and lupus. They identified a potential association between these groups when analysing genes in the JAK-STAT signalling pathway, reinforced by real-world clinical data from the US National Hospital Discharge Survey.
To check whether the JAK-STAT signalling pathway is involved in AD, the researchers then analysed RNA-seq data from >200 people with AD and a similar number of healthy individuals. This type of NGS data counts how many RNA copies of a specific gene is present, allowing researchers to accurately measure the expression levels of thousands of genes in parallel. Interestingly, these analyses revealed altered levels of JAK-STAT gene expression in people with AD. These observations were reinforced by experiments performed in cell and animal models of AD, which showed increased JAK-STAT gene expression after exposure of cells and animals to amyloid Beta, the main component of amyloid plaques found in the brains of people with AD.
