New cell population identified in Alzheimer's Disease allows better targeting of macrophage populations in treatment of neurodegeneration

11 October 2022 | Tuesday | News

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.  
Image Source : Public Domain

Image Source : Public Domain

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. 


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.

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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