How individual cell types in the brain contribute to Alzheimer's disease

November 28, 2019

SINGAPORE, 28 November - Alzheimer's disease is the most common form of dementia in the elderly, which is increasingly important to the disease burden in ageing societies like Singapore. Despite this and the myriad investments into research on the disease, there is currently no effective treatment and an effective drug is yet to be discovered.

Researchers led by Duke-NUS Medical School, in collaboration with Monash University, have now published a comprehensive and detailed study of gene expression changes in specific human brain cell types that are associated with progression of Alzheimer's disease. Leveraging the latest single-cell sequencing technology, the findings yield insights that may aid in scientists' pursuit of potential druggable gene targets for drug development.

"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."

Focusing on the need to study cell types other than neurons, the main type of cell found in the brain, the researchers applied an innovative single-nucleus RNA sequencing technology called DroNCSeq to cells from the brain's entorhinal cortex, sampled from both control and Alzheimer's disease brains, yielding a total of over 13,000 high quality nuclei that they could analyse for gene expression differences. The entorhinal cortex, together with the hippocampus, are the regions of the brain that scientists understand to be involved in processing and storing memories, perceiving time, and predicting the future.

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."

The study identified new subpopulations of cells present only in Alzheimer's disease patient brains as well as common and distinct networks of genes and functions that were coregulated across different types of cells. These results provide insights into the coordinated control of Alzheimer's disease risk genes and their cell type-specific contribution to disease susceptibility, and can ultimately help scientists identify potential gene targets for Alzheimer's disease drug development.

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 Alzheimer's disease brain.

Professor Patrick Casey, Senior Vice Dean at Duke-NUS, commented, "Alzheimer's disease affects not only the patient, but also their caregivers. It is a global disease with biological, social, psychological, and economic impacts that will only grow in importance with increasingly ageing populations around the world. This study underscores the important role technological innovation and data science can play not only in helping us to better understand the disease, but also to identify potential drug targets."
The research team are following up with further research on identified potential druggable genes.

Duke-NUS Medical School

Related Brain Articles from Brightsurf:

Glioblastoma nanomedicine crosses into brain in mice, eradicates recurring brain cancer
A new synthetic protein nanoparticle capable of slipping past the nearly impermeable blood-brain barrier in mice could deliver cancer-killing drugs directly to malignant brain tumors, new research from the University of Michigan shows.

Children with asymptomatic brain bleeds as newborns show normal brain development at age 2
A study by UNC researchers finds that neurodevelopmental scores and gray matter volumes at age two years did not differ between children who had MRI-confirmed asymptomatic subdural hemorrhages when they were neonates, compared to children with no history of subdural hemorrhage.

New model of human brain 'conversations' could inform research on brain disease, cognition
A team of Indiana University neuroscientists has built a new model of human brain networks that sheds light on how the brain functions.

Human brain size gene triggers bigger brain in monkeys
Dresden and Japanese researchers show that a human-specific gene causes a larger neocortex in the common marmoset, a non-human primate.

Unique insight into development of the human brain: Model of the early embryonic brain
Stem cell researchers from the University of Copenhagen have designed a model of an early embryonic brain.

An optical brain-to-brain interface supports information exchange for locomotion control
Chinese researchers established an optical BtBI that supports rapid information transmission for precise locomotion control, thus providing a proof-of-principle demonstration of fast BtBI for real-time behavioral control.

Transplanting human nerve cells into a mouse brain reveals how they wire into brain circuits
A team of researchers led by Pierre Vanderhaeghen and Vincent Bonin (VIB-KU Leuven, Université libre de Bruxelles and NERF) showed how human nerve cells can develop at their own pace, and form highly precise connections with the surrounding mouse brain cells.

Brain scans reveal how the human brain compensates when one hemisphere is removed
Researchers studying six adults who had one of their brain hemispheres removed during childhood to reduce epileptic seizures found that the remaining half of the brain formed unusually strong connections between different functional brain networks, which potentially help the body to function as if the brain were intact.

Alcohol byproduct contributes to brain chemistry changes in specific brain regions
Study of mouse models provides clear implications for new targets to treat alcohol use disorder and fetal alcohol syndrome.

Scientists predict the areas of the brain to stimulate transitions between different brain states
Using a computer model of the brain, Gustavo Deco, director of the Center for Brain and Cognition, and Josephine Cruzat, a member of his team, together with a group of international collaborators, have developed an innovative method published in Proceedings of the National Academy of Sciences on Sept.

Read More: Brain News and Brain Current Events is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to