ArticleEBioMedicine2020
Microglia facilitate loss of perineuronal nets in the Alzheimer's disease brain.
Article in EBioMedicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.
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Who cites it
161 citing papers in PubMed, 1 synthesis or guideline pooled it, 270 citations in OpenAlex.
- The impact of CSF1R inhibitor-mediated microglial depletion in rodent models of Alzheimer's and Parkinson's disease: a systematic review and meta-analysis.Frontiers in aging neuroscience · 2026Pooled it
- Ketamine preserves perineuronal nets in chronic stressed mice brain through the inhibition of microglia activation.IBRO neuroscience reports · 2026Article
- Parvalbumin interneurons in Alzheimer's disease: Physiological insights and pathophysiological mechanisms.Journal of cell communication and signaling · 2026Review
- Perineuronal Net and Inhibitory Synapse Remodeling on Striatal Fast-Spiking Interneurons by Chronic Alcohol Exposure.Biological psychiatry · 2026Article
- The role of Annexin A2 in Alzheimer's disease: From cellular functions to therapeutic potential.The FEBS journal · 2026Review
- Neuroinflammation in Alzheimer's and Parkinson's diseases: pathogenic mechanisms and therapeutic strategies.Translational neurodegeneration · 2026Review
- Molecular Basis of Glia-ECM Interplay in Central Nervous System Homeostasis and Plasticity.Cells · 2026Review
- Folic Acid and Endothelial Dysfunction in COVID-19.Life (Basel, Switzerland) · 2026Review
- 11-keto-β-boswellic acid and Z-guggulsterone suppress HMGB1/TLR4 pathway activity and modulate microglial polarization to remodel perineuronal nets after nerve injury.Journal of advanced research · 2026Article
- A dual role of hippocampal perineuronal nets in plasticity and protection is revealed by improvement and impairment of diet-induced memory dysfunction.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Extracellular matrix remodelling in neurological diseases.Nature reviews. Neurology · 2026Review
- Neuromodulatory role and therapeutic potential of N 6 -methyladenosine RNA methylation in neurodegenerative diseases.Neural regeneration research · 2026Article
- 4-methylumbelliferone attenuates amyloid pathology and learning deficits in the APP/PS1 mouse model.bioRxiv : the preprint server for biology · 2026Article
- Sex-dependent interferon signaling contributes to female-biased vulnerability in Alzheimer's disease.Journal of neuroinflammation · 2026Article
- Infection of 5xFAD mice with a mouse-adapted SARS-CoV-2 does not alter Alzheimer's disease neuropathology yet induces widespread changes in gene expression across diverse cell types.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Structural immunity: immune cells as architects of tissue barriers.Nature reviews. Immunology · 2026Review
- The NLRP3 Inflammasome in Neuropsychiatric Disorders: Molecular Mechanisms and Emerging Therapeutic Strategies.International journal of molecular sciences · 2026Review
- Neurotransmitter Systems in Alzheimer's Disease.Current issues in molecular biology · 2026Review
- Environmental Enrichment Preserves Retrosplenial Parvalbumin Density and Cognitive Function in Female 5xFAD Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Altered Microglia-Neuron Crosstalk and Regional Heterogeneity in Alzheimer's Disease Revealed by Single-Nucleus RNA Sequencing.International journal of molecular sciences · 2026Article
101 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
backgroundMicroglia, the brain's principal immune cell, are increasingly implicated in Alzheimer's disease (AD), but the molecular interfaces through which these cells contribute to amyloid beta (Aβ)-related neurodegeneration are unclear. We recently identified microglial contributions to the homeostatic and disease-associated modulation of perineuronal nets (PNNs), extracellular matrix structures that enwrap and stabilize neuronal synapses, but whether PNNs are altered in AD remains controversial.
methodsExtensive histological analysis was performed on male and female 5xFAD mice at 4, 8, 12, and 18 months of age to assess plaque burden, microgliosis, and PNNs. Findings were validated in postmortem AD tissue. The role of neuroinflammation in PNN loss was investigated via LPS treatment, and the ability to prevent or rescue disease-related reductions in PNNs was assessed by treating 5xFAD and 3xTg-AD model mice with colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 to deplete microglia.
findingsUtilizing the 5xFAD mouse model and human cortical tissue, we report that PNNs are extensively lost in AD in proportion to plaque burden. Activated microglia closely associate with and engulf damaged nets in the 5xFAD brain, and inclusions of PNN material are evident in mouse and human microglia, while aggrecan, a critical PNN component, deposits within human dense-core plaques. Disease-associated reductions in parvalbumin (PV)+ interneurons, frequently coated by PNNs, are preceded by PNN coverage and integrity impairments, and similar phenotypes are elicited in wild-type mice following microglial activation with LPS. Chronic pharmacological depletion of microglia prevents 5xFAD PNN loss, with similar results observed following depletion in aged 3xTg-AD mice, and this occurs despite plaque persistence.
interpretationWe conclude that phenotypically altered microglia facilitate plaque-dependent PNN loss in the AD brain.
fundingThe NIH (NIA, NINDS) and the Alzheimer's Association.
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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.