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Contributory Effects of Each Brain Cell Type in Development of Alzheimer’s Disease

Researchers from Duke-NUS Medical School and Monash University band together to bring the discovery of a treatment for Alzheimer’s disease closer with better identification of gene targets.

From the ESCAP Statisitcal Database, in 2016 Southeast Asia saw 9.6 percent of their population aged 60 years and older. This number is projected to increase to 21.1 percent by 2050. With a rapidly ageing population many age-related disease such as Alzheimer’s disease (AD) will become more prevalent. AD is the most common cause of dementia among the elderly, in 2015 there were 23 million people with dementia with an estimated cost of dementia care in the Asia Pacific region of US$185 billion. Despite the public health need and heavy investment in research for a treatment of AD, there is currently not effective drug that is able to treat AD.

The research team from Duke-NUS Medical School and Monash University leveraged on the latest single-cell sequencing technology to comprehensively study gene expression changes in specific human brain cell types found to be associated with AD.

“Limited information has been available about how individual cell types in the brain contribute to Alzheimer’s disease,” said study co-senior author Assistant Professor Owen Rackham, from Duke-NUS’ Cardiovascular and Metabolic Disorders (CVMD) Programme. “Although various genes have been implicated in Alzheimer’s disease, we do not know which cell types harbour these differences in gene expression.”

These findings will provide insight to aid scientists in the discovery of potential druggable gene targets for drug development. The researchers applied an innovative single-nucleus RNA sequencing technology called DroNCSeq to cells from the entorchinal cortex in the brain. This part of the brain is the main interface between the hippocampus and neocortex and is known to undergo pathological anatomical changes during AD. Sampled from both control and AD brains of over 13,000 high quality nuclei they could analyse differences in gene expression.

Associate Professor Enrico Petretto, co-senior author of the study, explained, “Our research sought to explore whether the answer to treating Alzheimer’s lies in understanding how non-neuronal cells are affected during the disease. Using DroNCSeq, we were able to study differences in gene expressions at single-cell resolution, which is key to understanding how genes identified by genome-wide association studies in specific cell subpopulations are associated with Alzheimer’s disease.”

To facilitate access to these insights by other researchers, the research team published an

interactive online tool to visualise and analyse their dataset, providing a unique resource for

future studies seeking to understand cellular differences and define functional changes at single-cell level in the human AD brain.

The team is looking to further the research to identify potential druggable genes.

The study was published in November 2019 on the scientific journal Nature Neuroscience[APBN]