The Microglial Component of Amyotrophic Lateral Sclerosis

Benjamin E. Clarke; Rickie Patani


Brain. 2020;143(12):3526-3539. 

In This Article

Evidence From Human ALS Tissue

Study of post-mortem tissue has provided an association between microglia and ALS. However, there has been some controversy over whether microglial activation from a ramified or stellate to an ameboid shape, increased proliferation and/or upregulation of inflammatory pathways, is present in post-mortem ALS tissue. While there have been some reports of microglial proliferation only occurring in a subset of ALS cases (Spiller et al., 2018; Tam et al., 2019), other studies have reported that microglia are activated in both the motor cortex (Dols-Icardo et al., 2020) and spinal cord (Brettschneider et al., 2012; D'Erchia et al., 2017) of sporadic ALS cases. Controversy over increases in microglial activation in ALS may be due to heterogeneity across different ALS genetic subtypes or perhaps due to artefacts in immunolabelling or degradation of post-mortem tissue. Furthermore, since microglia have been shown to undergo large changes in gene expression in normal brain ageing (Soreq et al., 2017), different ages of patients may affect the conclusions made from these studies.

Findings from post-mortem tissue are limited as they only provide a snapshot of pathology at the end stage of disease and are also, to some degree, affected by variable agonal phases and post-mortem intervals. These limitations have been overcome to some extent by monitoring neuroinflammation in living patients. To this end, advances in PET imaging have provided some information about longitudinal changes in neuroinflammation in ALS patients. Increased neuroinflammation has been observed in the primary and supplementary motor and temporal cortices of ALS patients using PET imaging of various ligands that bind to the immune marker, translocator protein 18 (TSPO) (Turner et al., 2004; Corcia et al., 2012; Alshikho et al., 2018). However, TSPO labels astrocytes and other immune cells in addition to microglia, making it impossible to delineate microglial specific effects. In summary, the study of ALS patients has so far only provided limited information concerning the specific involvement of microglia in ALS.