Abstract
Alzheimer’s disease (AD) is a lethal neurodegenerative disorder primarily affecting the aged population. The etiopathogenesis of AD, especially that of the sporadic type, remains elusive. The triggering receptor expressed on myeloid cells 2 (TREM2), a member of TREM immunoglobulin superfamily, plays a critical role in microglial physiology. Missense mutations in human TREM2 are determined as genetic risk factors associated with the development of sporadic AD. However, the roles of TREM2 in the pathogenesis of AD are still to be established. In this review, we outlined the influence of Trem2 on balance of pro- and anti-inflammatory microglial activations from a perspective of AD mouse model transcriptomics. On this basis, we further speculated the roles of TREM2 in different stages of AD, which may shed light to the development of TREM2-targeted strategy for the prevention and treatment of this neurodegenerative disorder.
Highlights
Alzheimer’s disease (AD) is a heterogeneous and chronic neurological disorder in which progressive cognitive decline and gradual neurodegeneration converge [1,2]
Mutations in genes encoding amyloid precursor protein (APP), presenilin 1 (PS1) and presenilin 2 (PS2) that promote amyloidosis and/or tauopathy are closely associated with the development of familial AD (FAD) [3,4]
Alongside Aβ plaque and neurofibrillary tangles (NFTs), the progressively developed chronic neuroinflammation is an important feature in FAD and sporadic AD (SAD) pathogenesis [5,6,7,8]
Summary
Alzheimer’s disease (AD) is a heterogeneous and chronic neurological disorder in which progressive cognitive decline and gradual neurodegeneration converge [1,2]. The cellular component enrichment analysis suggests the distribution of DAM markers in the extracellular space, lysosome, cell surface, melanosome, and external side of plasma membrane (p < 0.001) (Figure 2B) These DAM markers are proposed to be associated with the regulation of microglial chemotaxis, proteolysis, inflammatory response, and lysosome biosynthesis. The enrichment in innate immune pathways of the neurodegeneration-related modules included antigen presentation and endocytosis, while the depletion in pro-inflammatory activations included chemokines, complement system, and Il1 signaling (Figure 2F) This analysis added supportive evidence to the documented anti-inflammatory effects of Trem signaling [83,84]. The anti-inflammatory properties of Trem2-dependent DAM may be feeble because the genetic Trem depletion shows less effect on pro-inflammatory gene expression in some AD mouse models [37,61] In this regard, it is still unclear whether Trem modulation can influence pro- or anti-inflammatory microglial activations. Further patients-based studies may help to determine the roles of TREM2 in shaping microglial phenotypes and DAM functions in AD
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
