ArticleCell reports2024
Microglia degrade Alzheimer's amyloid-beta deposits extracellularly via digestive exophagy.
Article in Cell reports, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
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Who cites it
23 citing papers in PubMed.
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- High reelin expression may explain why a subgroup of entorhinal cortex neurons functions as an initial nucleation site of Alzheimer's disease.PLoS computational biology · 2026Article
- A novel autopolysialylation activity of the ganglioside sialyltransferase ST8Sia5 regulates its secretion and enzyme activity.The Journal of biological chemistry · 2026Article
- Neuroprotective effects of ursodeoxycholic acid in Parkinson's disease and Alzheimer's disease.Neuroprotection (Chichester, England) · 2026Review
- Microglial response to sleep deprivation depends on the hippocampal region and paradigm used in adult male mice.Brain, behavior, & immunity - health · 2026Article
- Inhibiting the transient receptor potential melastatin 2 channel in microglia: current evidence and therapeutic potential in neurological disorders.Acta pharmacologica Sinica · 2026Review
- Protocol for the quantification of digestive exophagy in cell culture.STAR protocols · 2026Article
- Plaque-associated Microglial Polarization in Visual Brain Regions of the 5xFAD Mouse Model.bioRxiv : the preprint server for biology · 2026Article
- Digging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis.Cellular and molecular neurobiology · 2026Review
- Mapping the Brain's Glymphatic System.Biomedicines · 2026Review
- Plaque-associated microglial polarization in visual brain regions of the 5xFAD mouse model.Frontiers in aging neuroscience · 2026Article
- Integrating brain organoids, meningeal immunity, and glymphatic dynamics: toward modeling neuroimmune clearance and crosstalk in disease.Frontiers in immunology · 2026Review
- Autophagy-lysosomal pathway in neurodegeneration.Molecular neurodegeneration advances · 2026Review
- Microglial phagocytosis in Alzheimer disease.Nature reviews. Neurology · 2026Review
- Microglial state transitions are constrained by developmental and metabolic checkpoints.Frontiers in cellular neuroscience · 2026Review
- Proteome-Based Biomarkers for Alzheimer's Disease: Old Acquisitions and Innovative Proposals.International journal of molecular sciences · 2025Review
- The Proteostasis Network in Proteinopathies: Mechanisms and Interconnections.The American journal of pathology · 2025Review
- Real-time pH imaging of macrophage lysosomes using the pH-sensitive probe ApHID.Cell reports methods · 2025Article
- HAPLN2 forms aggregates and promotes microglial inflammation during brain aging in mice.PLoS biology · 2025Article
- Article
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
How microglia digest Alzheimer's fibrillar amyloid-beta (Aβ) plaques that are too large to be phagocytosed is not well understood. Here, we show that primary microglial cells create acidic extracellular compartments, lysosomal synapses, on model plaques and digest them with exocytosed lysosomal enzymes. This mechanism, called digestive exophagy, is confirmed by electron microscopy in 5xFAD mouse brains, which shows that a lysosomal enzyme, acid phosphatase, is secreted toward the plaques in structures resembling lysosomal synapses. Signaling studies demonstrate that the PI3K-AKT pathway modulates the formation of lysosomal synapses, as inhibition of PI3K1β or AKT1/2 reduces both lysosome exocytosis and actin polymerization, both required for the formation of the compartments. Finally, we show that small fibrils of Aβ previously internalized and trafficked to lysosomes are exocytosed toward large Aβ aggregates by microglia. Thus, the release of lysosomal contents during digestive exophagy may also contribute to the spread and growth of fibrillar Aβ.
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What Socratic 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 Socratic graph.