ArticleJournal of Alzheimer's disease : JAD2018
Erythromyeloid-Derived TREM2: A Major Determinant of Alzheimer's Disease Pathology in Down Syndrome.
Article in Journal of Alzheimer's disease : JAD, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
24 citing papers in PubMed, 2 syntheses or guidelines pooled it, 33 citations in OpenAlex.
- Blood-based biomarkers for Alzheimer's disease in Down syndrome: A systematic review and meta-analysis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Pooled it
- Targeting TREM2 for Parkinson's Disease: Where to Go?Frontiers in immunology · 2021Pooled it
- An Altered Relationship between Soluble TREM2 and Inflammatory Markers in Young Adults with Down Syndrome: A Preliminary Report.Journal of immunology (Baltimore, Md. : 1950) · 2020Trial
- Microglial exosome TREM2 ameliorates ferroptosis and neuroinflammation in alzheimer's disease by activating the Wnt/β-catenin signaling.Scientific reports · 2025Article
- Exploring peripheral fluid biomarkers for early detection of Alzheimer's disease in Down syndrome: A literature review.Heliyon · 2025Review
- Clinical and research application of fluid biomarkers in autosomal dominant Alzheimer's disease and Down syndrome.EBioMedicine · 2024Review
- Exercise mimetics: a novel strategy to combat neuroinflammation and Alzheimer's disease.Journal of neuroinflammation · 2024Review
- TREM2 macrophages induced by human lipids drive inflammation in acne lesions.Science immunology · 2022Article
- Review
- Interplay of Ferritin Accumulation and Ferroportin Loss in Ageing Brain: Implication for Protein Aggregation in Down Syndrome Dementia, Alzheimer's, and Parkinson's Diseases.International journal of molecular sciences · 2022Article
- Astroglial and microglial pathology in Down syndrome: Focus on Alzheimer's disease.Frontiers in cellular neuroscience · 2022Review
- Impaired Iron Homeostasis and Haematopoiesis Impacts Inflammation in the Ageing Process in Down Syndrome Dementia.Journal of clinical medicine · 2021Article
- Maternal antibodies facilitate Amyloid-β clearance by activating Fc-receptor-Syk-mediated phagocytosis.Communications biology · 2021Article
- Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?Nature reviews. Neurology · 2021Review
- Hepcidin Increases Cytokines in Alzheimer's Disease and Down's Syndrome Dementia: Implication of Impaired Iron Homeostasis in Neuroinflammation.Frontiers in aging neuroscience · 2021Article
- The influence of the R47H triggering receptor expressed on myeloid cells 2 variant on microglial exosome profiles.Brain communications · 2021Article
- Investigation of CD26, a potential SARS-CoV-2 receptor, as a biomarker of age and pathology.Bioscience reports · 2020Article
- Evolution of neuroinflammation across the lifespan of individuals with Down syndrome.Brain : a journal of neurology · 2020Article
- Further understanding the connection between Alzheimer's disease and Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2020Review
- Investigation of pathology, expression and proteomic profiles in human TREM2 variant postmortem brains with and without Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundDown syndrome (DS; trisomy 21) individuals have a spectrum of hematopoietic and neuronal dysfunctions and by the time they reach the age of 40 years, almost all develop Alzheimer's disease (AD) neuropathology which includes senile plaques and neurofibrillary tangles. Inflammation and innate immunity are key players in AD and DS. Triggering receptor expressed in myeloid cells-2 (TREM2) variants have been identified as risk factors for AD and other neurodegenerative diseases.
objectiveTo investigate the effects of TREM2 and the AD-associated R47H mutation on brain pathology and hematopoietic state in AD and DS.
methodsWe analyzed peripheral blood, bone marrow, and brain tissue from DS, AD, and age-matched control subjects by immunohistochemistry and western blotting. TREM2-related phagocytosis was investigated using a human myeloid cell line.
resultsTREM2 protein levels in brain and sera declined with age and disease progression in DS. We observed soluble TREM2 in brain parenchyma that may be carried by a subset of microglia, macrophages, or exosomes. Two DS cases had the AD-associated TREM2-R47H mutation, which manifested a morphologically extreme phenotype of megakaryocytes and erythrocytes in addition to impaired trafficking of TREM2 to the erythroid membrane. TREM2 was shown to be involved in phagocytosis of red blood cells. TREM2 was seen in early and late endosomes. Silencing TREM2 using siRNA in THP1 cells resulted in significant cell death.
conclusionWe provide evidence that peripheral TREM2 originating from erythromyeloid cells significantly determines AD neuropathology in DS subjects. Understanding the molecular signaling pathways mediated by TREM2 may reveal novel therapeutic targets.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.