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Exploring the Disease-Associated Microglia State in Amyotrophic Lateral Sclerosis
Carlota Jauregui1, Idoia Blanco-Luquin2, Mónica Macías2
1Neurology Department, Hospital Universitario de Navarra (HUN), IdiSNA (Navarra Institute of Health Research), 31008 Pamplona, Spain.
Background:
Neuroinflammation, and specifically microglia, plays an important but not-yet well-understood role in the pathophysiology of amyotrophic lateral sclerosis (ALS), constituting a potential therapeutic target for the disease. Recent studies have described the involvement of different microglial transcriptional patterns throughout neurodegenerative processes, identifying a new state of microglia: disease-associated microglia (DAM). The aim of this study is to investigate expression patterns of microglial-related genes in ALS spinal cord.
Methods:
We analyzed mRNA expression levels via RT-qPCR of several microglia-related genes in their homeostatic and DAM state in postmortem tissue (anterior horn of the spinal cord) from 20 subjects with ALS-TDP43 and 19 controls donors from the Navarrabiomed Biobank.
Results:
The expression levels of TREM2, MS4A, CD33, APOE and TYROBP were found to be elevated in the spinal cord from ALS subjects versus controls (p-value < 0.05). However, no statistically significant gene expression differences were observed for TMEM119, SPP1 and LPL.
Conclusions:
This study suggests that a DAM-mediated inflammatory response is present in ALS, and TREM2 plays a significant role in immune function of microglia. It also supports the role of C33 and MS4A in the physiopathology of ALS.
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