ArticleJournal of visualized experiments : JoVE2016
Correlative Light and Electron Microscopy to Study Microglial Interactions with β-Amyloid Plaques.
Article in Journal of visualized experiments : JoVE, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- Digging Deep into Alzheimer Disease: How Electron Microscopy Helps Elucidating Its Pathogenesis.Cellular and molecular neurobiology · 2026Review
- Exploring Iron Deposition Patterns Using Light and Electron Microscopy in the Mouse Brain Across Aging and Alzheimer's Disease Pathology Conditions.Journal of neurochemistry · 2025Article
- Particulate matter and co-occurring genetic risk induce oxidative stress and cardiac and brain Alzheimer's pathology.Communications biology · 2025Article
- Microglia degrade Alzheimer's amyloid-beta deposits extracellularly via digestive exophagy.Cell reports · 2024Article
- Astrocytes display ultrastructural alterations and heterogeneity in the hippocampus of aged APP-PS1 mice and human post-mortem brain samples.Journal of neuroinflammation · 2023Article
- Ultrastructural characterization of dark microglia during aging in a mouse model of Alzheimer's disease pathology and in human post-mortem brain samples.Journal of neuroinflammation · 2022Article
- CX3CR1 deficiency aggravates amyloid driven neuronal pathology and cognitive decline in Alzheimer's disease.Molecular neurodegeneration · 2022Article
- Brain Ultrastructure: Putting the Pieces Together.Frontiers in cell and developmental biology · 2021Review
- Vascular contributions to 16p11.2 deletion autism syndrome modeled in mice.Nature neuroscience · 2020Article
- Atrx Deletion in Neurons Leads to Sexually Dimorphic Dysregulation of miR-137 and Spatial Learning and Memory Deficits.Cell reports · 2020Article
- Microglial physiological properties and interactions with synapses are altered at presymptomatic stages in a mouse model of Huntington's disease pathology.Journal of neuroinflammation · 2020Article
- Imaging the Neuroimmune Dynamics Across Space and Time.Frontiers in neuroscience · 2020Review
- Mitochondrial sub-cellular localization of cAMP-specific phosphodiesterase 8A in ovarian follicular cells.Scientific reports · 2019Article
- Gestational Stress Augments Postpartum β-Amyloid Pathology and Cognitive Decline in a Mouse Model of Alzheimer's Disease.Cerebral cortex (New York, N.Y. : 1991) · 2019Article
- Ultrastructural evidence of microglial heterogeneity in Alzheimer's disease amyloid pathology.Journal of neuroinflammation · 2019Article
- Microglial Ultrastructure in the Hippocampus of a Lipopolysaccharide-Induced Sickness Mouse Model.Frontiers in neuroscience · 2019Article
- Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral, Microglial, and Molecular Abnormalities Associated with Schizophrenia.Frontiers in molecular neuroscience · 2018Article
- A Brief History of Microglial Ultrastructure: Distinctive Features, Phenotypes, and Functions Discovered Over the Past 60 Years by Electron Microscopy.Frontiers in immunology · 2018Review
- Delta Opioid Receptor Signaling Promotes Resilience to Stress Under the Repeated Social Defeat Paradigm in Mice.Frontiers in molecular neuroscience · 2018Article
- Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A detailed protocol is provided here to identify amyloid Aβ plaques in brain sections from Alzheimer's disease mouse models before pre-embedding immunostaining (specifically for ionized calcium-binding adapter molecule 1 (IBA1), a calcium binding protein expressed by microglia) and tissue processing for electron microscopy (EM). Methoxy-X04 is a fluorescent dye that crosses the blood-brain barrier and selectively binds to β-pleated sheets found in dense core Aβ plaques. Injection of the animals with methoxy-X04 prior to sacrifice and brain fixation allows pre-screening and selection of the plaque-containing brain sections for further processing with time-consuming manipulations. This is particularly helpful when studying early AD pathology within specific brain regions or layers that may contain very few plaques, present in only a small fraction of the sections. Post-mortem processing of tissue sections with Congo Red, Thioflavin S, and Thioflavin T (or even with methoxy-X04) can label β-pleated sheets, but requires extensive clearing with ethanol to remove excess dye and these procedures are incompatible with ultrastructural preservation. It would also be inefficient to perform labeling for Aβ (and other cellular markers such as IBA1) on all brain sections from the regions of interest, only to yield a small fraction containing Aβ plaques at the right location. Importantly, Aβ plaques are still visible after tissue processing for EM, allowing for a precise identification of the areas (generally down to a few square millimeters) to examine with the electron microscope.
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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.