3D-Reconstruction of microglia and amyloid in APP23 transgenic mice: no evidence of intracellular amyloid
Abstract
Microglia cells are closely associated with compact amyloid plaques in Alzheimer's disease (AD) brains. Although activated microglia seem to play a central role in the pathogenesis of AD, mechanisms of microglial activation by beta-amyloid as well as the nature of interaction between amyloid and microglia remain poorly understood. We previously reported a close morphological association between activated microglia and congophilic amyloid plaques in the brains of APP23 transgenic mice at both the light and electron microscopic levels [25]. In the present study, we have further examined the structural relationship between microglia and amyloid deposits by using postembedding immunogold labeling, serial ultrathin sectioning, and 3-dimensional reconstruction. Although bundles of immunogold-labeled amyloid fibrils were completely engulfed by microglial cytoplasm on single sections, serial ultrathin sectioning and three-dimensional reconstruction revealed that these amyloid fibrils are connected to extracellular amyloid deposits. These data demonstrate that extracellular amyloid fibrils form a myriad of finger-like channels with the widely branched microglial cytoplasm. We conclude that in APP23 mice a role of microglia in amyloid phagocytosis and intracellular production of amyloid is unlikely.
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It remains unclear to what extent microglia are capable of removing amyloid from pre-existing fibrillar congophilic plaques or of preventing the deposition of smaller protofibrillar Aβ aggregates.
“it remains unclear to what extent microglia are capable of removing amyloid from pre-existing fibrillar congophilic plaques (Stalder et al., 2001) or of preventing the deposition of smaller protofibrillar Aβ aggregates (Grathwohl et al., 2009).”
From CX3CR1 in Microglia Regulates Brain Amyloid Deposition through Selective Protofibrillar Amyloid-β Phagocytosis (2010) · cites this paper as Stalder et al., 2001
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- Authors
- Stalder, M., Deller, T., Staufenbiel, M., & Jucker, M.
- Affiliations
- University of Basel (CH)
- Goethe University Frankfurt (DE)
- Novartis (Switzerland) (CH)
- Corresponding author
- Jucker, M
- Venue
- Neurobiology of Aging
- Publisher
- Elsevier BV
- Published
- 2001-05
- Volume
- 22
- Issue
- 3
- Pages
- 427-434
- ISSN
- 0197-4580 (ISSN-L)
- OpenAlex
- W1987595364
- Cited by
- 118
- References
- 5
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 4 · 2022: 4 · 2021: 1 · 2020: 4 · 2019: 2 · 2018: 1 · 2017: 3 · 2016: 8 · 2015: 7 · 2014: 1 · 2013: 9 · 2012: 8
- FWCI
- 3.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurobiology of Aging (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Neurological Disease Mechanisms and Treatments
- Keywords
- microglia, amyloid plaques, APP23 transgenic mice, Alzheimer's disease, amyloid-beta, amyloid fibrils, microglial activation, microglial morphology, immunogold labeling, 3D reconstruction
- MeSH terms
- Alzheimer Disease, Animals, Cytoplasm, Extracellular Space, Humans, Mice, Transgenic, Microscopy, Electron, Mutation, Ultrasonography, Amyloid beta-Protein Precursor, Microglia, Mice, Plaque, Amyloid
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