ArticleNature neuroscience2023
A TREM2-activating antibody with a blood-brain barrier transport vehicle enhances microglial metabolism in Alzheimer's disease models.
Article in Nature neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers.
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Who cites it
174 citing papers in PubMed, 214 citations in OpenAlex.
- MD2-IN-1 restores microglial lysosomal function and attenuates amyloid pathology through TREM2-associated signaling in 5×FAD mice.Acta pharmacologica Sinica · 2026Article
- Article
- Spatiotemporal heterogeneity and dynamic evolution of microglial glucose metabolic reprogramming in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- TREM2-mediated Crosstalk in ALS: Microglial Fate Transition, Protein Aggregate Clearance, and Peripheral Nerve Repair.Neuroscience bulletin · 2026Article
- Human Stem Cell-Derived Models of the Alzheimer's Disease Neuroimmune System.International journal of molecular sciences · 2026Review
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Microglial TDP-43 mediates myelin refinement and represses Tyrobp cryptic exon inclusion in mice.Nature neuroscience · 2026Article
- Neurodegenerative diseases and immune system: From pathogenic mechanism to therapy.Neural regeneration research · 2026Article
- Targeting Mitochondrial Dysfunction in Microglia: A New Frontier for Treating Neurodegenerative Diseases.Molecular neurobiology · 2026Review
- Determining the molecular and physiological actions of subtype-selective nanobodies of GABAScience advances · 2026Article
- Article
- TREM2 in neurodegenerative diseases and acute neurological injuries: mechanisms to targeted therapies.Cell communication and signaling : CCS · 2026Review
- Reduced LACTB expression in myeloid cells is associated with elevated succinylcarnitine and reduced Alzheimer's disease risk.Research square · 2026Article
- FcγR- and CD9-dependent synapse-engulfing microglia in the thalamus drive cognitive impairment following cortical brain damage in mice.Nature communications · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Translating genome-wide association studies at multiple scales: Drug target prioritization, cellular architectures, and organ imaging.Cell genomics · 2026Review
- CD98hc-targeted antibody shuttles for central nervous system delivery with broad cross-species reactivity.Nature biomedical engineering · 2026Article
- Microglial checkpoint collapse in Alzheimer's disease: a tri-axial framework for biomarker-informed neuroimmune therapy.Journal of neuroinflammation · 2026Review
- Antibody-oligonucleotide conjugates: an emerging modality for precision RNA therapeutics.Antibody therapeutics · 2026Review
- Non-canonical function of transferrin receptor-1 promotes breast cancer metastasis by activating HCK‒STAT3‒MMP9 signalling.Clinical and translational medicine · 2026Article
114 more citing papers are in PubMed but not listed here.
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Authors and funding
63 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Loss-of-function variants of TREM2 are associated with increased risk of Alzheimer's disease (AD), suggesting that activation of this innate immune receptor may be a useful therapeutic strategy. Here we describe a high-affinity human TREM2-activating antibody engineered with a monovalent transferrin receptor (TfR) binding site, termed antibody transport vehicle (ATV), to facilitate blood-brain barrier transcytosis. Upon peripheral delivery in mice, ATV:TREM2 showed improved brain biodistribution and enhanced signaling compared to a standard anti-TREM2 antibody. In human induced pluripotent stem cell (iPSC)-derived microglia, ATV:TREM2 induced proliferation and improved mitochondrial metabolism. Single-cell RNA sequencing and morphometry revealed that ATV:TREM2 shifted microglia to metabolically responsive states, which were distinct from those induced by amyloid pathology. In an AD mouse model, ATV:TREM2 boosted brain microglial activity and glucose metabolism. Thus, ATV:TREM2 represents a promising approach to improve microglial function and treat brain hypometabolism found in patients with AD.
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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.