ArticleJournal of neuroinflammation2022
Microglial VPS35 deficiency impairs Aβ phagocytosis and Aβ-induced disease-associated microglia, and enhances Aβ associated pathology.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 45 citations in OpenAlex.
- Levetiracetam restores GABAergic function and network homeostasis following Vps35 deficiency in excitatory neurons.Translational neurodegeneration · 2026Article
- Retromer-targeted therapy for neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Astrocytic VPS35 coordinates iron homeostasis with HIF1α-VEGFa signaling to prevent astrocytic ferroptosis and to promote neocortical angiogenesis.Cell & bioscience · 2026Article
- Oligodendrocyte precursor cells-microglia crosstalk via BMP4 drives microglial neuroprotective response and mitigates Alzheimer's disease.Signal transduction and targeted therapy · 2026Article
- Emerging pathological mechanisms of Alzheimer's disease pathogenesis: from neuroimmune interactions to intercellular communication.Frontiers in aging neuroscience · 2026Review
- The Impact of Neurotoxin Proteins Trafficked by Primary Cilia and Extracellular Vesicles in Neurodegenerative Diseases.Biology · 2025Review
- Uric Acid Functions as an Endogenous Modulator of Microglial Function and Amyloid Clearance in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Endothelial-Targeted Metallothionein-2 shRNA Nanoparticles Alleviate Migraine-Like Symptoms.CNS neuroscience & therapeutics · 2025Article
- Stabilizing the retromer complex rescues synaptic dysfunction and endosomal trafficking deficits in an Alzheimer's disease mouse model.Acta neuropathologica communications · 2025Article
- Article
- Hippocampal CA1 neuron, a crucial regulator for chronic stress exacerbating Alzheimer's disease progression.Cell & bioscience · 2025Article
- Asrij/OCIAD1 depletion reduces inflammatory microglial activation and ameliorates Aβ pathology in an Alzheimer's disease mouse model.Journal of neuroinflammation · 2025Article
- VPS35-Retromer: Multifunctional Roles in Various Biological Processes - A Focus on Neurodegenerative Diseases and Cancer.Journal of inflammation research · 2025Review
- Endosomal traffic disorders: a driving force behind neurodegenerative diseases.Translational neurodegeneration · 2024Review
- Haploinsufficiency and Alzheimer's Disease: The Possible Pathogenic and Protective Genetic Factors.International journal of molecular sciences · 2024Review
- Functional Relationships between L1CAM, LC3, ATG12, and Aβ.International journal of molecular sciences · 2024Article
- Microglial senescence in neurodegeneration: Insights, implications, and therapeutic opportunities.Neuroprotection (Chichester, England) · 2024Article
- VPS35 or retromer as a potential target for neurodegenerative disorders: barriers to progress.Expert opinion on therapeutic targets · 2024Review
- Intermittent hypoxia training enhances Aβ endocytosis by plaque associated microglia via VPS35-dependent TREM2 recycling in murine Alzheimer's disease.Alzheimer's research & therapy · 2024Article
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundVacuolar sorting protein 35 (VPS35), a key component of the retromer, plays an essential role in selectively retrieval of transmembrane proteins from endosomes to trans-Golgi networks. Dysfunctional retromer is a risk factor for neurodegenerative disorders, including Alzheimer's disease (AD). Microglial VPS35 deficiency is found in AD patients' brain; however, it remains unclear if and how microglial VPS35-loss contributes to AD development.
methodsWe used mice with VPS35 cKO (conditional knockout) in microglial cells in 5XFAD, an AD mouse model. The AD related brain pathology (Aβ and glial activation), behavior, and phagocytosis of Aβ were accessed by a combination of immunofluorescence staining analyses and neurological behavior tests.
resultsA decrease in learning and memory function, but increases in insoluble, fibrillar, and plaques of β-amyloids (Aβ), dystrophic neurites, and reactive astrocytes are observed in microglial VPS35 deficient 5XFAD mice. Further examining microglial phenotype demonstrates necessity of microglial VPS35 in disease-associated microglia (DAM) development and microglial uptake of Aβ, revealing a tight association of microglial Aβ uptake with DAM development.
conclusionsTogether, these results uncovered a mechanism by which microglial VPS35-deficiency precipitates AD pathology in 5XFAD mice likely by impairing DAM development and DAM mediated Aβ uptake and clearance, and thus accelerating the cognition decline.
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Registered trials
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