Abstract
Alzheimer’s disease (AD) is the leading cause of age-related dementia among the elderly population. Recent genetic studies have identified rare variants of the gene encoding the triggering receptor expressed on myeloid cells-2 (TREM2) as significant genetic risk factors in late-onset AD (LOAD). TREM2 is specifically expressed in brain microglia and modulates microglial functions in response to key AD pathologies such as amyloid-β (Aβ) plaques and tau tangles. In this review article, we discuss recent research progress in our understanding on the role of TREM2 in microglia and its relevance to AD pathologies. In addition, we discuss evidence describing new TREM2 ligands and the role of TREM2 signaling in microglial survival and energy metabolism. A comprehensive understanding of TREM2 function in the pathogenesis of AD offers a unique opportunity to explore the potential of this microglial receptor as an alternative target in AD therapy.
Highlights
Alzheimer’s disease (AD) is the leading cause of age-related dementia among the elderly population
Genetic variants of the triggering receptor expressed on myeloid cells-2 (TREM2), which is dominantly expressed in microglia in central nervous system (CNS), result in increased risk of developing late-onset AD (LOAD) and other neurodegenerative disorders (Guerreiro et al, 2013; Jonsson et al, 2013; Painter et al, 2015; Ulrich and Holtzman, 2016)
We discuss recent progress in our understanding of the role of TREM2 in microglia functions related to AD pathology, as well as signaling pathways activated by TREM2 ligands and their role in microglial survival and metabolism
Summary
AD is pathologically characterized by a buildup of extracellular senile plaques composed of Aβ peptide, intracellular NFTs composed of hyperphosphorylated tau (p-tau) protein and reactive gliosis, including microgliosis (Efthymiou and Goate, 2017; Leyns and Holtzman, 2017). Soluble β-amyloid precursor protein (APP), Aβ, tau and p-tau in cerebrospinal fluid and blood are candidate biomarkers for AD (Hampel et al, 2010; Shekhar et al, 2016; Lucey et al, 2017; Tatebe et al, 2017)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
