Dec 17, 2014

The triggering receptor expressed on myeloid cells 2 (TREM2) is associated with enhanced inflammation, neuropathological lesions and increased risk for Alzheimer's dementia

Alzheimer's & Dementia : the Journal of the Alzheimer's Association
Panos RoussosV Haroutunian

Abstract

The objective of this study was to elucidate the relationship between the triggering receptor expressed on myeloid cells 2 (TREM2) risk variant, neuropathological lesions, alterations in gene and protein expression, and the severity of neuroinflammation. The genetic association study of the R47 H TREM2 variant with Alzheimer's disease (AD), neuropathology, and changes in TREM2 and TYRO protein tyrosine kinase-binding protein (TYROBP) gene and protein expression, and neuroinflammatory markers. The TREM2 variant is associated with: (i) AD (odds ratio: 4.76; P = .014); (ii) increased density of amyloid plaques and neurofibrillary tangles in multiple brain regions; (iii) increased TREM2 (P = .041) and TYROBP (P = .006) gene expression; (iv) decreased TREM2 protein levels (P = .016); and (v) upregulation of proinflammatory cytokines (regulated on activation, normal T cell expressed and secreted [RANTES] and interferon [IFN] gamma) (P = .003) and nominal downregulation of protective markers (α2-macroglobulin, interleukin 4 or IL-4, and ApoA1) (P = .018). These findings link the TREM2 missense mutation with specific molecular abnormalities and increases in neuropathological lesions in the human brain.

  • References47
  • Citations11

References

  • References47
  • Citations11

Citations

Mentioned in this Paper

Real-Time Polymerase Chain Reaction
Familial Alzheimer Disease (FAD)
T-Lymphocyte
Tumor Necrosis Factor-alpha
APP protein, human
Systemic Inflammatory Response Syndrome
Apolipoprotein E4
Interleukin-7
Neurofibrillary Degeneration (Morphologic Abnormality)
Immunodeficiency due to Defect in MAPBP-Interacting Protein

Related Feeds

Alzheimer's Disease: Abeta

Alzheimer's disease (AD) is a chronic neurodegenerative disease associated with accumulation of amyloid plaques, which are comprised of amyloid beta. Here is the latest research in this field.

Alzheimer's Disease: Early Markers

Alzheimer's disease is a chronic neurodegenerative disease. This feed focuses on early markers, as well as environmental, pharmacological, and drug-response biomarkers associated with this disease.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's Disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's Disease here.

Alzheimer's Disease: APP

Amyloid precursor protein proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques. Here is the latest research.

Alzheimer's Disease: RNA Sequencing

RNA sequencing is used to reveal the presence and quantity of RNA in a given sample. In this feed, RNA sequencing investigates the genetic and molecular mechanisms related to the pathophysiology of Alzheimer's disease (AD). Here are the latest discoveries pertaining to RNA sequencing and this disease.

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Alzheimer's Disease: Genes&Microglia

Genes and microglia are associated with the risk of developing and the progression of conditions such as Alzheimer's Disease (AD). Here are the latest discoveries pertaining to this disease.

Alzheimer's Disease: Transcription

Transcription involves copying (transcribing) the gene's DNA sequence into RNA. Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and this disease.

Alzheimer's Disease: Genetics

Alzheimer's disease is a chronic neurodegenerative disease. Discover genetic and epigenetic aspects of Alzheimer’s disease, including genetic markers and genomic structural variations here.

Alzheimer's Disease: Neuroimaging

Alzheimer's disease (AD) is a chronic neurodegenerative disease. Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.