Exploring the Disease-Associated Microglia State in Amyotrophic Lateral Sclerosis
2023
Carlota Jauregui | Idoia Blanco-Luquin | Mónica Macías | Miren Roldan | Cristina Caballero | Inma Pagola | Maite Mendioroz | Ivonne Jericó
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 <i>TREM2</i>, <i>MS4A</i>, <i>CD33</i>, <i>APOE</i> and <i>TYROBP</i> were found to be elevated in the spinal cord from ALS subjects versus controls (<i>p</i>-value < 0.05). However, no statistically significant gene expression differences were observed for <i>TMEM119</i>, <i>SPP1</i> and <i>LPL</i>. Conclusions: This study suggests that a DAM-mediated inflammatory response is present in ALS, and <i>TREM2</i> plays a significant role in immune function of microglia. It also supports the role of <i>C33</i> and <i>MS4A</i> in the physiopathology of ALS.
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