ArticleThe Journal of experimental medicine2023
Chronic TREM2 activation exacerbates Aβ-associated tau seeding and spreading.
Article in The Journal of experimental medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
98 citing papers in PubMed, 2 syntheses or guidelines pooled it, 134 citations in OpenAlex.
- Gain-of-function Modulation of TREM2 and its Impact on Amyloid-β and Tau Pathologies in Alzheimer's Disease: A Systematic Review and Meta-analysis of Animal Studies.Molecular neurobiology · 2026Pooled it
- Association of soluble TREM2 with Alzheimer's disease and mild cognitive impairment: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2024Pooled it
- Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer's disease.Alzheimer's research & therapy · 2024Trial
- Context-dependent TREM2 signalling in myeloid cells: Molecular mechanisms and immunotherapeutic divergence in neurodegeneration and cancer.Clinical and translational medicine · 2026Review
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Microglia-mediated synaptic pruning in neural circuit remodeling: multidimensional control in homeostasis and neuropathology.BMC medicine · 2026Review
- TREM2 in neurodegeneration and diseases.Molecular psychiatry · 2026Review
- Distinct factors drive the progression of tau pathology in Alzheimer's disease.Fundamental research · 2026Review
- Microglial ITAM & ITIM Signaling in Neurodegenerative Disease and Brain Aging.Journal of molecular biology · 2026Review
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Microglia-Astrocyte Cooperation and Peripheral T Cells in Alzheimer's Disease: State-of-the-Art and Treatment Perspectives.International journal of molecular sciences · 2026Review
- Dietary Bioactives in Alzheimer's Disease: A Critical Appraisal of Clinical Trials and Future Nutritional Strategies.Nutrients · 2026Review
- Phagocytosis and neuroinflammation: orchestrating central nervous system homeostasis, repair, and the resolution of inflammation.Trends in neurosciences · 2026Review
- Immune dysfunction in Alzheimer disease.Nature reviews. Neuroscience · 2026Review
- A ligand-mimetic anti-TREM2 agonist antibody elevates soluble TREM2 and ameliorates pathology in mouse models of Alzheimer's disease and multiple sclerosis.Journal of neuroinflammation · 2026Article
- BMAL1-GPX3 axis in the choroid plexus mitigates Aβ pathology in an amyloid mouse model.Journal of neuroinflammation · 2026Article
- Neuroinflammation at the Crossroads of Neurodegeneration: The Roles of Microglia and Astrocytes in Parkinson's Disease, Alzheimer's Disease, and Multiple Sclerosis.Neurosciences (Riyadh, Saudi Arabia) · 2026Review
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Spatially resolved transcriptomic profiling identifies distinct signatures in parenchymal and vascular microenvironments in Alzheimer's Disease with Cerebral Amyloid Angiopathy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuroimmune Interactions in Neurodegeneration: The Role of Microglia in Alzheimer's and Parkinson's Disease Pathogenesis.Brain sciences · 2026Review
38 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Variants in the triggering receptor expressed on myeloid cells 2 (TREM2) gene are associated with increased risk for late-onset AD. Genetic loss of or decreased TREM2 function impairs the microglial response to amyloid-β (Aβ) plaques, resulting in more diffuse Aβ plaques and increased peri-plaque neuritic dystrophy and AD-tau seeding. Thus, microglia and TREM2 are at a critical intersection of Aβ and tau pathologies in AD. Since genetically decreasing TREM2 function increases Aβ-induced tau seeding, we hypothesized that chronically increasing TREM2 signaling would decrease amyloid-induced tau-seeding and spreading. Using a mouse model of amyloidosis in which AD-tau is injected into the brain to induce Aβ-dependent tau seeding/spreading, we found that chronic administration of an activating TREM2 antibody increases peri-plaque microglial activation but surprisingly increases peri-plaque NP-tau pathology and neuritic dystrophy, without altering Aβ plaque burden. Our data suggest that sustained microglial activation through TREM2 that does not result in strong amyloid removal may exacerbate Aβ-induced tau pathology, which may have important clinical implications.
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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.