ArticleNature communications2024
BHLHE40/41 regulate microglia and peripheral macrophage responses associated with Alzheimer's disease and other disorders of lipid-rich tissues.
Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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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.
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Who cites it
37 citing papers in PubMed, 41 citations in OpenAlex.
- An aging-sensitive secreted phospholipase confers neuroprotection and cognitive resilience.Nature neuroscience · 2026Article
- Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Modulation of neuronal excitability and plasticity by BHLHE41 conveys lithium non-responsiveness.Molecular psychiatry · 2026Article
- Youth-associated protein TIMP2 regulates microglial state and function in healthy and aged mice.Nature communications · 2026Article
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- Lung adenocarcinoma cell-derived lactate activates CAFs to promote macrophage M2 polarization via exosomal miR-214-5p.Oncogenesis · 2026Article
- Atherosclerosis Profiling Reveals BHLHE40 as a Candidate Modulator of VSMC.Circulation research · 2026Article
- Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.Nature communications · 2026Article
- Impaired lipoprotein secretion by APOE4 leads to lysosomal and mitochondrial dysfunction in human microglia.bioRxiv : the preprint server for biology · 2026Article
- MEF2C controls lysosomal and lipid clearance programs linked to Alzheimer's disease risk in macrophages.Research square · 2026Article
- Aurka-Bhlhe41 axis prevents premature aging-like microglial dysfunction and promotes remyelination.Nature communications · 2026Article
- Phagocytes as plaque catalysts: Human macrophages generate seeding-competent Aβ42 fibrils with cross-seeding activity.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Genetic variations interact with polybrominated diphenyl ether exposure to alter lipid homeostasis.Nature communications · 2026Article
- 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
- APOE4-driven T cell dysregulation in Alzheimer's disease: single-cell genomics and Mendelian randomization reveal novel therapeutic targets.Journal of neuroinflammation · 2026Article
- Comparative lipidomics of iPSC-derived microglia protocols reveal lipid droplet and immune differences mediated by media composition.Stem cell reports · 2026Article
- Early microglial priming in Alzheimer's disease revealed by ME-seq.bioRxiv : the preprint server for biology · 2026Article
- Reply to: a quantitative trait locus for reduced microglial APOE expression associates with reduced cerebral amyloid angiopathy.Nature genetics · 2026Article
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Genetic and experimental evidence suggests that Alzheimer's disease (AD) risk alleles and genes may influence disease susceptibility by altering the transcriptional and cellular responses of macrophages, including microglia, to damage of lipid-rich tissues like the brain. Recently, sc/nRNA sequencing studies identified similar transcriptional activation states in subpopulations of macrophages in aging and degenerating brains and in other diseased lipid-rich tissues. We collectively refer to these subpopulations of microglia and peripheral macrophages as DLAMs. Using macrophage sc/nRNA-seq data from healthy and diseased human and mouse lipid-rich tissues, we reconstructed gene regulatory networks and identified 11 strong candidate transcriptional regulators of the DLAM response across species. Loss or reduction of two of these transcription factors, BHLHE40/41, in iPSC-derived microglia and human THP-1 macrophages as well as loss of Bhlhe40/41 in mouse microglia, resulted in increased expression of DLAM genes involved in cholesterol clearance and lysosomal processing, increased cholesterol efflux and storage, and increased lysosomal mass and degradative capacity. These findings provide targets for therapeutic modulation of macrophage/microglial function in AD and other disorders affecting lipid-rich tissues.
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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.