Exploring the Disease-Associated Microglia State in Amyotrophic Lateral Sclerosis

Carlota Jauregui; Idoia Blanco-Luquin; Mónica Macías; Miren Roldan; Cristina Caballero; Inma Pagola; Maite Mendioroz; Ivonne Jericó

doi:10.3390/biomedicines11112994

Exploring the Disease-Associated Microglia State in Amyotrophic Lateral Sclerosis

Biomedicines. 2023 Nov 8;11(11):2994. doi: 10.3390/biomedicines11112994.

Authors

Carlota Jauregui¹, Idoia Blanco-Luquin², Mónica Macías², Miren Roldan², Cristina Caballero³, Inma Pagola^{1

4}, Maite Mendioroz^{1

2}, Ivonne Jericó^{1

4}

Affiliations

¹ Neurology Department, Hospital Universitario de Navarra (HUN), IdiSNA (Navarra Institute of Health Research), 31008 Pamplona, Spain.
² Neuroepigenetics Laboratory, Navarrabiomed, Universidad Pública de Navarra (UPNA), IdiSNA (Navarra Institute of Health Research), 31008 Pamplona, Spain.
³ Department of Pathology, Hospital Universitario de Navarra (HUN), IdiSNA (Navarra Institute of Health Research), 31008 Pamplona, Spain.
⁴ Neuromuscular and Neuron Motor Diseases Research Group, Navarrabiomed, IdiSNA (Navarra Institute of Health Research), 31008 Pamplona, Spain.

Abstract

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.

Keywords: CD33; MS4A; amyotrophic lateral sclerosis; disease-associated microglia; neurodegeneration; neuroinflammation.

Grants and funding

This work was supported by donations from ANELA (Navarra ALS Association). Framework between ANELA and Miguel Servet Foundation/Navarrabiomed was signed on 17 December 2014.