Should We Open Fire on Microglia? Depletion Models as Tools to Elucidate Microglial Role in Health and Alzheimer’s Disease

Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model

(2021) Kevin Clayton et al.   Molecular Neurodegeneration

Microglia use TAM receptors to detect and engulf amyloid β plaques

(2021) Youtong Huang et al.   NATURE IMMUNOLOGY

Evolving Models and Tools for Microglial Studies in the Central Nervous System

(2021) Yang Zhang et al.   Neuroscience Bulletin

Replicative senescence dictates the emergence of disease-associated microglia and contributes to Aβ pathology

(2021) Yanling Hu et al.   Cell Reports

The role of P2Y12 in the kinetics of microglial self-renewal and maturation in the adult visual cortex in vivo

(2021) Monique S Mendes et al.   eLife

CSF1R inhibition rescues tau pathology and neurodegeneration in an A/T/N model with combined AD pathologies, while preserving plaque associated microglia

(2021) Chritica Lodder et al.   Acta Neuropathologica Communications

Infiltration of CD163-positive macrophages in glioma tissues after treatment with anti-PD-L1 antibody and role of PI3Kγ inhibitor as a combination therapy with anti-PD-L1 antibody in in vivo model using temozolomide-resistant murine glioma-initiating cells

(2020) Tsubasa Miyazaki et al.   Brain Tumor Pathology

Dystrophic microglia in late‐onset Alzheimer's disease

(2020) Wolfgang J. Streit et al.   GLIA

Absence of microglia or presence of peripherally‐derived macrophages does not affect tau pathology in young or old hTau mice

(2020) Keying Zhu et al.   GLIA

Plaque-associated myeloid cells derive from resident microglia in an Alzheimer’s disease model

(2020) Erin G. Reed-Geaghan et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Human and mouse single-nucleus transcriptomics reveal TREM2-dependent and TREM2-independent cellular responses in Alzheimer’s disease

(2020) Yingyue Zhou et al.   NATURE MEDICINE

Astrocytes and Microglia: In Sickness and in Health

(2020) Ilia D. Vainchtein et al.   TRENDS IN NEUROSCIENCES

Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion

(2020) Jason R. Plemel et al.   Science Advances

Defining molecular identity and fates of CNS-border associated macrophages after ischemic stroke in rodents and humans

(2020) Wenson D. Rajan et al.   NEUROBIOLOGY OF DISEASE

Microglia depletion rapidly and reversibly alters amyloid pathology by modification of plaque compaction and morphologies

(2020) Brad T. Casali et al.   NEUROBIOLOGY OF DISEASE

Microglial depletion aggravates the severity of acute and chronic seizures in mice

(2020) Wenning Wu et al.   BRAIN BEHAVIOR AND IMMUNITY

Inhibition of Colony-Stimulating Factor 1 Receptor by PLX3397 Prevents Amyloid Beta Pathology and Rescues Dopaminergic Signaling in Aging 5xFAD Mice

(2020) Yeonghoon Son et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Anti-human TREM2 induces microglia proliferation and reduces pathology in an Alzheimer’s disease model

(2020) Shoutang Wang et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Integrated analysis of ultra-deep proteomes in cortex, cerebrospinal fluid and serum reveals a mitochondrial signature in Alzheimer’s disease

(2020) Hong Wang et al.   Molecular Neurodegeneration

To Kill a Microglia: A Case for CSF1R Inhibitors

(2020) Kim N. Green et al.   TRENDS IN IMMUNOLOGY

Microglia depletion diminishes key elements of the leukotriene pathway in the brain of Alzheimer’s Disease mice

(2020) J. Michael et al.   Acta Neuropathologica Communications

APOE and TREM2 regulate amyloid-responsive microglia in Alzheimer’s disease

(2020) Aivi T. Nguyen et al.   ACTA NEUROPATHOLOGICA

Astrocytic phagocytosis is a compensatory mechanism for microglial dysfunction

(2020) Hiroyuki Konishi et al.   EMBO JOURNAL

CSF1R inhibition by a small-molecule inhibitor is not microglia specific; affecting hematopoiesis and the function of macrophages

(2020) Fengyang Lei et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Translating genetic risk of Alzheimer’s disease into mechanistic insight and drug targets

(2020) Annerieke Sierksma et al.   SCIENCE

A MAC2-positive progenitor-like microglial population is resistant to CSF1R inhibition in adult mouse brain

(2020) Lihong Zhan et al.   eLife

Identification of a dysfunctional microglial population in human Alzheimer’s disease cortex using novel single-cell histology image analysis

(2020) Molly E. V. Swanson et al.   Acta Neuropathologica Communications

Microglia in Alzheimer’s Disease in the Context of Tau Pathology

(2020) Juan Ramón Perea et al.   Biomolecules

Amyloid‐β impairs the phagocytosis of dystrophic synapses by astrocytes in Alzheimer's disease

(2020) Maria V. Sanchez‐Mico et al.   GLIA

Neuroinflammation and microglial activation in Alzheimer disease: where do we go from here?

(2020) Fangda Leng et al.   Nature Reviews Neurology

Proximal recolonization by self-renewing microglia re-establishes microglial homeostasis in the adult mouse brain

(2019) Lihong Zhan et al.   PLOS BIOLOGY

Spatial and temporal heterogeneity of mouse and human microglia at single-cell resolution

(2019) Takahiro Masuda et al.   NATURE

Single-cell transcriptomic analysis of Alzheimer’s disease

(2019) Hansruedi Mathys et al.   NATURE

TREM2 function impedes tau seeding in neuritic plaques

(2019) Cheryl E. G. Leyns et al.   NATURE NEUROSCIENCE

CSF1R inhibitor JNJ-40346527 attenuates microglial proliferation and neurodegeneration in P301S mice

(2019) Renzo Mancuso et al.   BRAIN

Fragmented mitochondria released from microglia trigger A1 astrocytic response and propagate inflammatory neurodegeneration

(2019) Amit U. Joshi et al.   NATURE NEUROSCIENCE

Microglia drive APOE-dependent neurodegeneration in a tauopathy mouse model

(2019) Yang Shi et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Microglial regional heterogeneity and its role in the brain

(2019) Yun-Long Tan et al.   MOLECULAR PSYCHIATRY

A single-cell atlas of entorhinal cortex from individuals with Alzheimer’s disease reveals cell-type-specific gene expression regulation

(2019) Alexandra Grubman et al.   NATURE NEUROSCIENCE

Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer’s disease model

(2019) Elizabeth Spangenberg et al.   Nature Communications

Disease-Associated Microglia: A Universal Immune Sensor of Neurodegeneration

(2018) Aleksandra Deczkowska et al.   CELL

Toward a New Concept of Alzheimer’s Disease Models: A Perspective from Neuroinflammation

(2018) Antonia Gutierrez et al.   JOURNAL OF ALZHEIMERS DISEASE

Peripherally derived macrophages can engraft the brain independent of irradiation and maintain an identity distinct from microglia

(2018) James C. Cronk et al.   JOURNAL OF EXPERIMENTAL MEDICINE

Early long-term administration of the CSF1R inhibitor PLX3397 ablates microglia and reduces accumulation of intraneuronal amyloid, neuritic plaque deposition and pre-fibrillar oligomers in 5XFAD mouse model of Alzheimer’s disease

(2018) Justyna Sosna et al.   Molecular Neurodegeneration

Repopulated microglia are solely derived from the proliferation of residual microglia after acute depletion

(2018) Yubin Huang et al.   NATURE NEUROSCIENCE

Notch Signaling Regulates Microglial Activation and Inflammatory Reactions in a Rat Model of Temporal Lobe Epilepsy

(2018) Lei Wu et al.   NEUROCHEMICAL RESEARCH

Amyloid toxicity in Alzheimer’s disease

(2018) Allison B. Reiss et al.   REVIEWS IN THE NEUROSCIENCES

Tau passive immunization blocks seeding and spread of Alzheimer hyperphosphorylated Tau-induced pathology in 3 × Tg-AD mice

(2018) Chun-ling Dai et al.   Alzheimers Research & Therapy

Diverse Brain Myeloid Expression Profiles Reveal Distinct Microglial Activation States and Aspects of Alzheimer’s Disease Not Evident in Mouse Models

(2018) Brad A. Friedman et al.   Cell Reports

Microglia in Alzheimer’s Disease: Activated, Dysfunctional or Degenerative

(2018) Victoria Navarro et al.   Frontiers in Aging Neuroscience

Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation

(2018) Yikui Zhang et al.   Science Advances

Gantenerumab: A Novel Human Anti-Aβ Antibody Demonstrates Sustained Cerebral Amyloid-β Binding and Elicits Cell-Mediated Removal of Human Amyloid-β

(2018) Bernd Bohrmann et al.   JOURNAL OF ALZHEIMERS DISEASE

The role of microglia in processing and spreading of bioactive tau seeds in Alzheimer’s disease

(2018) Sarah C. Hopp et al.   Journal of Neuroinflammation

A limited capacity for microglial repopulation in the adult brain

(2018) Allison R. Najafi et al.   GLIA

CD11a expression distinguishes infiltrating myeloid cells from plaque-associated microglia in Alzheimer's disease

(2018) Ankita K. Shukla et al.   GLIA

Enforced microglial depletion and repopulation as a promising strategy for the treatment of neurological disorders

(2018) Jinming Han et al.   GLIA

Partial reduction of microglia does not affect tau pathology in aged mice

(2018) Rachel E. Bennett et al.   Journal of Neuroinflammation

Microglia and early brain development: An intimate journey

(2018) Morgane S. Thion et al.   SCIENCE

Distinct Microglial Responses in Two Transgenic Murine Models of TAU Pathology

(2018) Carmen Romero-Molina et al.   Frontiers in Cellular Neuroscience

Competitive repopulation of an empty microglial niche yields functionally distinct subsets of microglia-like cells

(2018) Harald Lund et al.   Nature Communications

Engrafted parenchymal brain macrophages differ from microglia in transcriptome, chromatin landscape and response to challenge

(2018) Anat Shemer et al.   Nature Communications

Microglial repopulation resolves inflammation and promotes brain recovery after injury

(2017) Rachel A. Rice et al.   GLIA

Bioenergetic regulation of microglia

(2017) Soumitra Ghosh et al.   GLIA

Depletion of microglia exacerbates postischemic inflammation and brain injury

(2017) Wei-Na Jin et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

Microglia limit the expansion of β-amyloid plaques in a mouse model of Alzheimer’s disease

(2017) Ruohe Zhao et al.   Molecular Neurodegeneration

TREM2 deficiency exacerbates tau pathology through dysregulated kinase signaling in a mouse model of tauopathy

(2017) Shane M. Bemiller et al.   Molecular Neurodegeneration

Microglia-derived ASC specks cross-seed amyloid-β in Alzheimer’s disease

(2017) Carmen Venegas et al.   NATURE

Amyloid-β plaques enhance Alzheimer's brain tau-seeded pathologies by facilitating neuritic plaque tau aggregation

(2017) Zhuohao He et al.   NATURE MEDICINE

Transcriptomic analysis of purified human cortical microglia reveals age-associated changes

(2017) Thais F Galatro et al.   NATURE NEUROSCIENCE

Diverse Requirements for Microglial Survival, Specification, and Function Revealed by Defined-Medium Cultures

(2017) Christopher J. Bohlen et al.   NEURON

Glial Cells and Their Function in the Adult Brain: A Journey through the History of Their Ablation

(2017) Sarah Jäkel et al.   Frontiers in Cellular Neuroscience

The Lifespan and Turnover of Microglia in the Human Brain

(2017) Pedro Réu et al.   Cell Reports

Coupled Proliferation and Apoptosis Maintain the Rapid Turnover of Microglia in the Adult Brain

(2017) Katharine Askew et al.   Cell Reports

Soluble phospho-tau from Alzheimer’s disease hippocampus drives microglial degeneration

(2016) Elisabeth Sanchez-Mejias et al.   ACTA NEUROPATHOLOGICA

Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology

(2016) Adrian Olmos-Alonso et al.   BRAIN

Eliminating microglia in Alzheimer’s mice prevents neuronal loss without modulating amyloid-β pathology

(2016) Elizabeth E. Spangenberg et al.   BRAIN

Early and protective microglial activation in Alzheimer’s disease: a prospective study using18F-DPA-714 PET imaging

(2016) Lorraine Hamelin et al.   BRAIN

Colony stimulating factor 1 receptor inhibition eliminates microglia and attenuates brain injury after intracerebral hemorrhage

(2016) Minshu Li et al.   JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM

The antibody aducanumab reduces Aβ plaques in Alzheimer’s disease

(2016) Jeff Sevigny et al.   NATURE

Emerging Roles for CSF-1 Receptor and its Ligands in the Nervous System

(2016) Violeta Chitu et al.   TRENDS IN NEUROSCIENCES

Microglia protect against brain injury and their selective elimination dysregulates neuronal network activity after stroke

(2016) Gergely Szalay et al.   Nature Communications

Dynamics of spinal microglia repopulation following an acute depletion

(2016) Yao Yao et al.   Scientific Reports

Elimination of microglia improves cognitive function following cranial irradiation

(2016) Munjal M. Acharya et al.   Scientific Reports

Reactive microglia drive tau pathology and contribute to the spreading of pathological tau in the brain

(2015) Nicole Maphis et al.   BRAIN

TREM2 Lipid Sensing Sustains the Microglial Response in an Alzheimer’s Disease Model

(2015) Yaming Wang et al.   CELL

Genetic Cell Ablation Reveals Clusters of Local Self-Renewing Microglia in the Mammalian Central Nervous System

(2015) Julia Bruttger et al.   IMMUNITY

Colony-stimulating factor 1 receptor inhibition prevents microglial plaque association and improves cognition in 3xTg-AD mice

(2015) Nabil N. Dagher et al.   Journal of Neuroinflammation

Depletion of microglia and inhibition of exosome synthesis halt tau propagation

(2015) Hirohide Asai et al.   NATURE NEUROSCIENCE

Orally administered colony stimulating factor 1 receptor inhibitor PLX3397 in recurrent glioblastoma: an Ivy Foundation Early Phase Clinical Trials Consortium phase II study

(2015) Nicholas Butowski et al.   NEURO-ONCOLOGY

Hypersialylation is a common feature of neurofibrillary tangles and granulovacuolar degenerations in Alzheimer's disease and tauopathy brains

(2015) Shun Nagamine et al.   NEUROPATHOLOGY

Targeting cells of the myeloid lineage attenuates pain and disease progression in a prostate model of bone cancer

(2015) Michelle L. Thompson et al.   PAIN

Structure and Assembly Mechanism of the Signaling Complex Mediated by Human CSF-1

(2015) Jan Felix et al.   STRUCTURE

Microglia constitute a barrier that prevents neurotoxic protofibrillar Aβ42 hotspots around plaques

(2015) Carlo Condello et al.   Nature Communications

Microglial internalization and degradation of pathological tau is enhanced by an anti-tau monoclonal antibody

(2015) Wenjie Luo et al.   Scientific Reports

Characterizing Newly Repopulated Microglia in the Adult Mouse: Impacts on Animal Behavior, Cell Morphology, and Neuroinflammation

(2015) Monica R. P. Elmore et al.   PLoS One

Environment Drives Selection and Function of Enhancers Controlling Tissue-Specific Macrophage Identities

(2014) David Gosselin et al.   CELL

Colony-Stimulating Factor 1 Receptor Signaling Is Necessary for Microglia Viability, Unmasking a Microglia Progenitor Cell in the Adult Brain

(2014) Monica R.P. Elmore et al.   NEURON

A Phenotypic Change But Not Proliferation Underlies Glial Responses in Alzheimer Disease

(2013) Alberto Serrano-Pozo et al.   AMERICAN JOURNAL OF PATHOLOGY

Profile of gantenerumab and its potential in the treatment of Alzheimer's disease

(2013) Robert Nisticò et al.   Drug Design Development and Therapy

Sensitive quantitative assays for tau and phospho-tau in transgenic mouse models

(2012) Christopher M. Acker et al.   NEUROBIOLOGY OF AGING

Microglial repopulation model reveals a robust homeostatic process for replacing CNS myeloid cells

(2012) N. H. Varvel et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structural Basis for the Dual Recognition of Helical Cytokines IL-34 and CSF-1 by CSF-1R

(2012) Xiaolei Ma et al.   STRUCTURE

Mechanism of Amyloid Removal in Patients With Alzheimer Disease Treated With Gantenerumab

(2011) Susanne Ostrowitzki   ARCHIVES OF NEUROLOGY

Microglial Cells Contribute to Endogenous Brain Defenses after Acute Neonatal Focal Stroke

(2011) J. V. Faustino et al.   JOURNAL OF NEUROSCIENCE

Absence of Colony Stimulation Factor-1 Receptor Results in Loss of Microglia, Disrupted Brain Development and Olfactory Deficits

(2011) Bryna Erblich et al.   PLoS One

Extracellular Complexes of the Hematopoietic Human and Mouse CSF-1 Receptor Are Driven by Common Assembly Principles

(2011) Jonathan Elegheert et al.   STRUCTURE

Regulation of Tau Pathology by the Microglial Fractalkine Receptor

(2010) Kiran Bhaskar et al.   NEURON

Fate Mapping Analysis Reveals That Adult Microglia Derive from Primitive Macrophages

(2010) F. Ginhoux et al.   SCIENCE

Colony-Stimulating Factor-1 Receptor Inhibitors for the Treatment of Cancer and Inflammatory Disease

(2009) Sharmila Patel et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Hypothetical model of dynamic biomarkers of the Alzheimer's pathological cascade

(2009) Clifford R Jack et al.   LANCET NEUROLOGY

Formation and maintenance of Alzheimer's disease β-amyloid plaques in the absence of microglia

(2009) Stefan A Grathwohl et al.   NATURE NEUROSCIENCE

Inflammatory Response in the Hippocampus of PS1M146L/APP751SL Mouse Model of Alzheimer's Disease: Age-Dependent Switch in the Microglial Phenotype from Alternative to Classic

(2008) S. Jimenez et al.   JOURNAL OF NEUROSCIENCE