The innate immune response in tauopathies

Abstract

Tauopathies, which include frontotemporal dementia, Alzheimer's disease, and chronic traumatic encephalopathy, are a class of neurological disorders resulting from pathogenic tau aggregates. These aggregates disrupt neuronal health and function leading to the cognitive and physical decline of tauopathy patients. Genome‐wide association studies and clinical evidence have brought to light the large role of the immune system in inducing and driving tau‐mediated pathology. More specifically, innate immune genes are found to harbor tauopathy risk alleles, and innate immune pathways are upregulated throughout the course of disease. Experimental evidence has expanded on these findings by describing pivotal roles for the innate immune system in the regulation of tau kinases and tau aggregates. In this review, we summarize the literature implicating innate immune pathways as drivers of tauopathy.

Galectin‐3 is upregulated in frontotemporal dementia patients with subtype specificity

“…A relevant maker of microglial activation in disease conditions is TREM2, which is implicated in the neuroinflammatory response in AD, and has shown a strong association with FTD-tau. [45][46][47][48] We demonstrated TA B L E 3 Multiple linear regression coefficients for assessing the different CSF biomarkers trajectories by CSF Gal-3 level according to age and sex. previously that Gal-3 expressed by microglial cells can act as a TREM2 ligand.…”

“…Due to FTD's substantial heterogeneity, significant differences emerged among clinical, genetic, and neuropathological subtypes. A relevant maker of microglial activation in disease conditions is TREM2, which is implicated in the neuroinflammatory response in AD, and has shown a strong association with FTD‐tau 45–48 . We demonstrated previously that Gal‐3 expressed by microglial cells can act as a TREM2 ligand 21 .…”

“…A relevant maker of microglial activation in disease conditions is TREM2, which is implicated in the neuroinflammatory response in AD, and has shown a strong association with FTD‐tau. 45 , 46 , 47 , 48 We demonstrated previously that Gal‐3 expressed by microglial cells can act as a TREM2 ligand. 21 In addition, we have shown a clear association of Gal‐3 with tau and p‐tau181 in CSF in AD and have demonstrated a clear co‐localization of microglial cells expressing Gal‐3 with tau protein in association of Aβ plaques.…”

Tau induces inflammasome activation and microgliosis through acetylating NLRP3

“…[33][34][35] There is mounting evidence indicating that inflammasome activation in microglia is pivotal for the pathogenesis of Tauopathies. 36,37 However, the mechanism by which Tau drives NLRP3 inflammasome activation is unknown. Canonical full activation of the NLRP3 inflammasome is regulated by a two-step process consisting of a priming step at the transcriptional and posttranslational levels, and an activation/assembly step.…”