ArticleScience translational medicine2025
Systematic analysis of cellular cross-talk reveals a role for SEMA6D-TREM2 regulating microglial function in Alzheimer's disease.
Article in Science translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
14 citing papers in PubMed.
- Phytoestrogens and related microbial metabolites remodel aberrant prostate transcriptomic profiles generated upon exposure to oxidative stress.Molecular and cellular biochemistry · 2026Article
- Dysregulated adult hippocampal neurogenesis in major depressive disorder.Nature medicine · 2026Article
- Genetic Associations with Temporal Modeling of Alzheimer's Disease Progression Supports a Novel Paradigm for Disease Risk.medRxiv : the preprint server for health sciences · 2026Article
- Deciphering microenvironmental heterogeneity by scalable Niche Guided Module Discovery.Communications biology · 2026Article
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Genetic modifiers of APOE-ε4-associated cognitive decline.Nature communications · 2026Article
- Neuronal guidance signaling in neurodegenerative diseases: Key regulators that function at neuron-glia and neuroimmune interfaces.Neural regeneration research · 2026Article
- Differential downstream signaling in microglia lacking Alzheimer's-related TREM2 or its adaptor TYROBP/DAP12.Molecular neurodegeneration advances · 2026Article
- Nutritional substrates and microglial metabolic fitness in brain aging and Alzheimer's disease: from lipid handling to TREM2-linked translation.Frontiers in nutrition · 2026Review
- Revisiting TREM2: from multi-omics signaling networks to clinical translation.Frontiers in immunology · 2026Review
- Evaluation of altered cell-cell communication between glia and neurons in the hippocampus of 3xTg-AD mice at two time points.bioRxiv : the preprint server for biology · 2024Article
- Altered glia-neuron communication in Alzheimer's Disease affects WNT, p53, and NFkB Signaling determined by snRNA-seq.Cell communication and signaling : CCS · 2024Article
- Altered Glia-Neuron Communication in Alzheimer's Disease Affects WNT, p53, and NFkB Signaling Determined by snRNA-seq.bioRxiv : the preprint server for biology · 2024Article
- Antibody elution methods for multiplex immunofluorescence of Alzheimer's disease pathology in human post-mortem brain tissue.Frontiers in neurologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
31 authors.
Funding
Abstract
Cellular cross-talk, mediated by membrane receptors and their ligands, is crucial for brain homeostasis and can contribute to neurodegenerative diseases such as Alzheimer's disease (AD). To find cross-talk dysregulations involved in AD, we reconstructed cross-talk networks from single-nucleus transcriptional profiles of 67 clinically and neuropathologically well-characterized controls and AD brain donors from the Knight Alzheimer Disease Research Center and the Dominantly Inherited Alzheimer Network cohorts. We predicted a role for TREM2 and additional AD risk genes mediating neuron-microglia cross-talk in AD. We identified a gene network mediating neuron-microglia cross-talk through TREM2 and neuronal SEMA6D, which we predicted is disrupted in late AD stages. Using spatial transcriptomics on the human brain, we observed that the SEMA6D-TREM2 cross-talk gene network is activated near Aβ plaques and SEMA6D-expressing cells. Using tissue immunostaining of human brains, we found that SEMA6D colocalizes with Aβ plaques and TREM2-activated microglia. In addition, we found that plaque-proximal SEMA6D abundance decreased with the disease stage, which correlated with a reduction in microglial activation near plaques. These findings suggest that the loss of SEMA6D signaling impairs microglial activation and Αβ clearance. To validate this hypothesis, we leveraged
Indexed as
Identifiers
What OpenQuestion holds
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.