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TREM2 brain transcript-specific studies in AD and TREM2 mutation carriers

Published on Dec 1, 2019in Molecular Neurodegeneration 8.27
· DOI :10.1186/s13024-019-0319-3
Jorge L. Del-Aguila8
Estimated H-index: 8
(WashU: Washington University in St. Louis),
Bruno A. Benitez15
Estimated H-index: 15
(WashU: Washington University in St. Louis)
+ 12 AuthorsCarlos Cruchaga48
Estimated H-index: 48
Cite
Abstract
Background Low frequency coding variants in TREM2 are associated with Alzheimer disease (AD) risk and cerebrospinal fluid (CSF) TREM2 protein levels are different between AD cases and controls. Similarly, TREM2 risk variant carriers also exhibit differential CSF TREM2 levels. TREM2 has three different alternative transcripts, but most of the functional studies only model the longest transcript. No studies have analyzed TREM2 expression levels or alternative splicing in brains from AD and cognitively normal individuals. We wanted to determine whether there was differential expression of TREM2 in sporadic-AD cases versus AD-TREM2 carriers vs sex- and aged-matched normal controls; and if this differential expression was due to a particular TREM2 transcript.
  • References (67)
  • Citations (1)
Cite
References67
Newest
Published on Dec 1, 2018in Genome Medicine 10.89
Zeran Li2
Estimated H-index: 2
(WashU: Washington University in St. Louis),
Jorge L. Del-Aguila8
Estimated H-index: 8
(WashU: Washington University in St. Louis)
+ 12 AuthorsJin-Moo Lee41
Estimated H-index: 41
(WashU: Washington University in St. Louis)
Alzheimer’s disease (AD) is characterized by neuronal loss and astrocytosis in the cerebral cortex. However, the specific effects that pathological mutations and coding variants associated with AD have on the cellular composition of the brain are often ignored. We developed and optimized a cell-type-specific expression reference panel and employed digital deconvolution methods to determine brain cellular distribution in three independent transcriptomic studies. We found that neuronal and astrocy...
Published on Dec 1, 2018in Molecular Neurodegeneration 8.27
Xianyuan Xiang4
Estimated H-index: 4
(LMU: Ludwig Maximilian University of Munich),
Thomas M. Piers5
Estimated H-index: 5
(UCL: University College London)
+ 10 AuthorsJochen Herms51
Estimated H-index: 51
(LMU: Ludwig Maximilian University of Munich)
Background The R47H variant of the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) significantly increases the risk for late onset Alzheimer’s disease. Mouse models accurately reproducing phenotypes observed in Alzheimer’ disease patients carrying the R47H coding variant are required to understand the TREM2 related dysfunctions responsible for the enhanced risk for late onset Alzheimer’s disease.
Published on Aug 10, 2018in Journal of Biological Chemistry
Athena Sudom15
Estimated H-index: 15
(Amgen),
Santosh Talreja5
Estimated H-index: 5
(Amgen)
+ 16 AuthorsEdoardo Marcora1
Estimated H-index: 1
(Amgen)
Published on Aug 6, 2018in Frontiers in Cellular Neuroscience 3.90
Hiroyuki Konishi13
Estimated H-index: 13
,
Hiroshi Kiyama50
Estimated H-index: 50
Microglia are activated after neuronal injury and in neurodegenerative diseases, and trigger neuroinflammation in the central nervous system. Microglia-derived neuroinflammation has both beneficial and detrimental effects on neurons. Because the timing and magnitude of microglial activation is thought to be a critical determinant of neuronal fate, understanding the molecular mechanisms underlying microglial activation is required to enable establishment of microglia-targeted therapies for neural...
Published on Jul 3, 2018in Expert Opinion on Therapeutic Targets 4.62
Yuetiva Deming8
Estimated H-index: 8
(WashU: Washington University in St. Louis),
Zeran Li2
Estimated H-index: 2
(WashU: Washington University in St. Louis)
+ 1 AuthorsCarlos Cruchaga48
Estimated H-index: 48
ABSTRACTIntroduction: There are currently no effective therapeutics for Alzheimer disease (AD). Clinical trials targeting amyloid beta thus far have shown very little benefit and only in the earliest stages of disease. These limitations have driven research to identify alternative therapeutic targets, one of the most promising is the triggering receptor expressed on myeloid cells 2 (TREM2).Areas covered: Here, we review the literature to-date and discuss the potentials and pitfalls for targeting...
Published on Jun 20, 2018in bioRxiv
Yuetiva Deming8
Estimated H-index: 8
(UW: University of Washington),
Fabia Filipello1
Estimated H-index: 1
(UW: University of Washington)
+ 33 AuthorsJ. A. Bradley12
Estimated H-index: 12
(UW: University of Washington)
Soluble triggering receptor expressed on myeloid cells 2 (sTREM2) levels in the cerebrospinal fluid (CSF) have been associated with Alzheimer disease (AD) status. TREM2 plays a critical role in microglial activation, survival, and phagocytosis; however, the pathophysiological role of sTREM2 in AD is not well understood. Understanding the role of sTREM2 in AD may help reveal biological mechanisms underlying AD and identify novel therapeutic targets. We performed a genome-wide association study (G...
Published on Mar 5, 2018in Journal of Experimental Medicine 10.89
Wilbur Song8
Estimated H-index: 8
(WashU: Washington University in St. Louis),
Satoru Joshita21
Estimated H-index: 21
(Shinshu University)
+ 3 AuthorsMarco Colonna4
Estimated H-index: 4
(WashU: Washington University in St. Louis)
Published on Mar 1, 2018in Neuron 14.40
Yingjun Zhao11
Estimated H-index: 11
(DI: Discovery Institute),
Xilin Wu2
Estimated H-index: 2
(Fujian Medical University)
+ 13 AuthorsMuxian Zhang3
Estimated H-index: 3
(Ha Tai: Xiamen University)
Summary Mutations in triggering receptor expressed on myeloid cells 2 ( TREM2 ) have been linked to increased Alzheimer's disease (AD) risk. Neurobiological functions of TREM2 and its pathophysiological ligands remain elusive. Here we found that TREM2 directly binds to β-amyloid (Aβ) oligomers with nanomolar affinity, whereas AD-associated TREM2 mutations reduce Aβ binding. TREM2 deficiency impairs Aβ degradation in primary microglial culture and mouse brain. Aβ-induced microglial depolarization...
Published on Feb 20, 2018in Journal of Alzheimer's Disease 3.70
Jorge L. Del-Aguila8
Estimated H-index: 8
(WashU: Washington University in St. Louis),
Maria Victoria Fernandez7
Estimated H-index: 7
(WashU: Washington University in St. Louis)
+ 13 AuthorsJoanne Norton22
Estimated H-index: 22
(WashU: Washington University in St. Louis)
Cited By1
Newest
Published on Jul 11, 2019in bioRxiv
Dimitra Sarantopoulou1
Estimated H-index: 1
(UPenn: University of Pennsylvania),
Soumyashant Nayak2
Estimated H-index: 2
(UPenn: University of Pennsylvania)
+ 2 AuthorsGregory R. Grant22
Estimated H-index: 22
(UPenn: University of Pennsylvania)
Full-length isoform quantification from RNA-Seq is a key goal in transcriptomics analyses and an area of active development. The fundamental difficulty stems from the fact that RNA transcripts are long, while RNA-Seq reads are typically short. We have generated realistic benchmarking data, and have performed a comprehensive comparative analysis of isoform quantification, including evaluating them on the level of differential expression analysis. Genome, transcriptome and pseudo alignment-based m...