New research has found a novel way to identify genes that are implicated in the neurodegenerative disorder known as Alzheimer’s disease using gene-network tools.
Using gene-network tools, researchers from Osaka University, Niigata University, and the National Center for Geriatrics and Gerontology have revealed genes that trigger specific changes in connections between proteins, called protein domain networks (PDNs), that are significantly associated with neurodegeneration in Alzheimer’s disease.
The study was published in Human Molecular Genetics.
The researchers conducted network analysis of changes in PDNs to determine whether this process could be used to reveal genetic changes associated with Alzheimer’s disease pathology throughout the different stages of the disease.
The researchers wanted to see if they could use an integrated network approach to identify new genes associated with the collapse of PDNs. To do this, the researchers examined protein interaction data and gene expression data from post-mortem brain samples from patients with Alzheimer’s disease to generate PDNs. They found that the deterioration of PDNs occurred at specific stages of Alzheimer’s disease and identified RAC1 as a specific gene that plays a key role in the alteration of PDNs. They then examined the effects of deactivating RAC1 in the fruit fly Drosophila.
Senior author, Koichi Iijima, said: “We found reduced levels of RAC1 in post-mortem brain samples from patients with Alzheimer’s disease, and these changes were validated by gene expression levels from a publicly available data set.”
“Further, inhibiting RAC1 in Drosophila induced age-dependent changes in behaviour, accompanied by neurodegeneration.”
In addition, they found that the number of interactions constituting PDNs in three regions from AD brains decreased with each stage of the disease.
Norikazu Hara, co-lead author, said: “These data provide further evidence that PDNs collapse during the progression of Alzheimer’s disease. Thus, changes in PDNs may be a key element of neuronal dysfunction and neurodegeneration that occurs in Alzheimer’s disease.”
This approach may improve the chances of uncovering new biomarkers and therapeutic treatments.