PMID- 30038567
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230926
IS  - 1663-4365 (Print)
IS  - 1663-4365 (Electronic)
IS  - 1663-4365 (Linking)
VI  - 10
DP  - 2018
TI  - TREM2-Dependent Effects on Microglia in Alzheimer's Disease.
PG  - 202
LID - 10.3389/fnagi.2018.00202 [doi]
LID - 202
AB  - Alzheimer's disease (AD) is a late-onset dementia characterized by the deposition 
      of amyloid plaques and formation of neurofibrillary tangles (NFTs) which lead to 
      neuronal loss and cognitive deficits. Abnormal protein aggregates in the AD brain 
      are also associated with reactive microglia and astrocytes. Whether this glial 
      response is beneficial or detrimental in AD pathology is under debate. Microglia 
      are the resident innate immune cells in the central nervous system (CNS) that 
      survey the surrounding environment. Genome-wide association studies (GWAS) have 
      identified the R47H variant of triggering receptor expressed on myeloid cell 2 
      (TREM2) as a risk factor for late-onset AD (LOAD) with an odds ratio of 4.5. 
      TREM2 is an immunoreceptor primarily present on microglia in the CNS that binds 
      to polyanionic molecules. The transmembrane domain of TREM2 signals through 
      DAP12, an adaptor protein that contains an immunoreceptor tyrosine-based 
      activation motif (ITAM), which mediates TREM2 signaling and promotes microglial 
      activation and survival. In mouse models of AD, Trem2 haplodeficiency and 
      deficiency lead to reduced microglial clustering around amyloid beta (Abeta) plaques, 
      suggesting TREM2 is required for plaque-associated microglial responses. 
      Recently, TREM2 has been shown to enhance microglial metabolism through the 
      mammalian target of rapamycin (mTOR) pathway. Although aberrant metabolism has 
      long been associated with AD, not much was known regarding how metabolism in 
      microglia might affect disease progression. In this review, we discuss the role 
      of TREM2 and metabolism in AD pathology, highlighting how TREM2-mediated 
      microglial metabolism modulates AD pathogenesis.
FAU - Zhou, Yingyue
AU  - Zhou Y
AD  - Department of Pathology and Immunology, Washington University in St. Louis, St. 
      Louis, MO, United States.
FAU - Ulland, Tyler K
AU  - Ulland TK
AD  - Department of Pathology and Immunology, Washington University in St. Louis, St. 
      Louis, MO, United States.
FAU - Colonna, Marco
AU  - Colonna M
AD  - Department of Pathology and Immunology, Washington University in St. Louis, St. 
      Louis, MO, United States.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180709
PL  - Switzerland
TA  - Front Aging Neurosci
JT  - Frontiers in aging neuroscience
JID - 101525824
PMC - PMC6046445
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - TREM2
OT  - autophagy
OT  - metabolism
OT  - microglia
EDAT- 2018/07/25 06:00
MHDA- 2018/07/25 06:01
PMCR- 2018/01/01
CRDT- 2018/07/25 06:00
PHST- 2018/04/05 00:00 [received]
PHST- 2018/06/13 00:00 [accepted]
PHST- 2018/07/25 06:00 [entrez]
PHST- 2018/07/25 06:00 [pubmed]
PHST- 2018/07/25 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fnagi.2018.00202 [doi]
PST - epublish
SO  - Front Aging Neurosci. 2018 Jul 9;10:202. doi: 10.3389/fnagi.2018.00202. 
      eCollection 2018.