New Cell Population Identified In Alzheimer's Disease

SINGAPORE – An Immunity research study has found that the previously identified disease-associated microglia (DAM) population detected in murine Alzheimer’s disease models actually contained an additional population of macrophages recruited during ageing and disease that exhibit inflammatory features, named disease inflammatory macrophages (DIMs). This new cell population was identified by a team of international scientists led by A*STAR’s Singapore Immunology Network (SIgN), with the study published on 9 August 2022.

Previously perceived as one population, this discovery of two different cell populations will allow for a better targeting—whether to mobilise the beneficial cell population or block the detrimental one—of relevant macrophage populations in the treatment of neurodegeneration.

In order to determine the two distinct cell populations, the team collected published single cell RNA-seq data sets on the brain in homeostasis, brain development and brain disease, and integrated these with their own data to generate a single cell universe from development to disease. This refined mapping of cell types was focused on the macrophages of the brain, which led to the discovery of the two regions.

They found that the DAM population emerges during neurodegenerative diseases in a TREM2 dependent manner and appear to be beneficial in clearing of amyloid beta and tissue repair, using a gene programme identified during normal brain development.

On the other hand, the DIM population emerges during ageing and neurodegenerative diseases in a TREM2 independent manner. They derive from monocytes infiltrating the brain through aging and diseases and express an inflammatory program, suggesting a detrimental functions.

ASTAR SIgNThe DAM population corresponds to a fetal-like reprogramming similar to Youth-Associated Microglia while DIMs appear during aging and increase in neurodegenerative diseases. (Image credit: A*STAR’s Singapore Immunology Network (SIgN))

These cell populations have been proven to exist in the human brain as well.

Lastly, the study highlights the potential opposite roles of macrophage populations in the brain, and could lead to the redefining of future strategies that will propose innovative treatment for neurodegenerative diseases, specifically targeting DIMs to reduce their inflammatory responses as well as promoting DAM to repair brain damages.

Dr Florent Ginhoux, Senior Principal Investigator at A*STAR’s SIgN and lead author of the study, said, “Our approach sheds light on brain macrophage heterogeneity and identified a cell population accumulating during ageing and neurodegeneration with proinflammatory features. Targeting this population may offer new therapeutic opportunities for Alzheimer’s Disease as well as other brain inflammatory diseases.”

Prof Lam Kong Peng, Executive Director at A*STAR’s SIgN, said, “Singapore faces increasing life expectancy and a rapidly ageing population, and diseases like Alzheimer’s can be expected to rise. This highly innovative research has great relevance to our efforts to understand the aging process, delay the onset of neurological diseases as well as enhance the mental and overall well-being of our population, and will provide greater insight for the development of targeted therapeutics and better healthcare outcomes.”

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About A*STAR’s Singapore Immunology Network (SIgN)

The Singapore Immunology Network (SIgN) is a research consortium established in 2006 under the Agency for Science, Technology and Research (A*STAR)’s Biomedical Research Council. The mission of SIgN is to advance human translational immunology research, contribute scientific knowledge and make innovative discoveries in immune-based therapeutics and technologies so as to improve lives and further socio-economic growth. SIgN is home to ~150 researchers comprising of renowned Principal Investigators, post-doctoral fellows and support staff working under the directorship of Professor Lam Kong Peng. SIgN also contributes to nurturing and retaining research talents to help build up the research ecosystem in Singapore.

SIgN research activities are broadly categorized into three main focus areas: Immuno-Oncology, Immune Potential, Regulation & Ageing and Immuno-Pathology. Our research groups are supported by a strong in-house cluster of cutting-edge technology platforms. Through partnership with hospitals and companies, SIgN is also committed to translate research findings into clinical and commercial applications. All in all, SIgN is working towards contributing to an enriching and vibrant research environment in Singapore.

For more information about SIgN, please visit www.a-star.edu.sg/sign.

About the Agency for Science, Technology and Research (A*STAR)

A*STAR is Singapore's lead public sector R&D agency. Through open innovation, we collaborate with our partners in both the public and private sectors to benefit the economy and society. As a Science and Technology Organisation, A*STAR bridges the gap between academia and industry. Our research creates economic growth and jobs for Singapore, and enhances lives by improving societal outcomes in healthcare, urban living, and sustainability. A*STAR plays a key role in nurturing scientific talent and leaders for the wider research community and industry. A*STAR’s R&D activities span biomedical sciences to physical sciences and engineering, with research entities primarily located in Biopolis and Fusionopolis.

For ongoing news, visit www.a-star.edu.sg.