Microglia contribute to the propagation of Aβ into unaffected brain tissue
Open accessAbstract
Microglia appear activated in the vicinity of amyloid beta (Aβ) plaques, but whether microglia contribute to Aβ propagation into unaffected brain regions remains unknown. Using transplantation of wild-type (WT) neurons, we show that Aβ enters WT grafts, and that this is accompanied by microglia infiltration. Manipulation of microglia function reduced Aβ deposition within grafts. Furthermore, in vivo imaging identified microglia as carriers of Aβ pathology in previously unaffected tissue. Our data thus argue for a hitherto unexplored mechanism of Aβ propagation.
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Our results are in line with studies showing that reduced microglial colocalization with β-amyloid is associated with a reduced β-amyloid burden.
“Our results are in line with studies showing that reduced microglial colocalization with β-amyloid is associated with a reduced β-amyloid burden (D’Errico et al., 2022; Spangenberg et al., 2019).”
From A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation (2023) · cites this paper as D’Errico et al., 2022
The Main section (page not provided) reports less microglial clustering around Aβ plaques and fewer amyloid deposits in wild-type grafts when microglial migration into those grafts was reduced. But the mice had similar numbers of Aβ plaques in the surrounding host tissue, so the finding supports reduced graft deposition, not a general reduction in Aβ burden. (LLM, conf=0.87)
Experimental — accuracy not yet measuredMicroglia have been suggested to deposit plaques in non-burdened brain tissue.
“Microglia have as well been suggested to deposit plaques in non-burdened brain tissue (D’Errico et al., 2022).”
From A novel molecular class that recruits HDAC/MECP2 complexes to PU.1 motifs reduces neuroinflammation (2023) · cites this paper as D’Errico et al., 2022
The activation of microglia by protein aggregates creates a feed-forward vicious cycle that aggravates neurodegeneration as activated microglia contribute to the propagation of tau, Aβ, α-synuclein, and TDP-43 into unaffected brain regions.
“Ultimately, the activation of microglia by these protein aggregates creates a feed-forward vicious cycle that aggravates neurodegeneration as activated microglia contribute to the propagation of tau, Aβ, α-synuclein, and TDP-43 into unaffected brain regions.159–164”
From Microbiota–gut–brain axis and its therapeutic applications in neurodegenerative diseases (2024) · cites this paper as [160]
Microglia facilitate Aβ spreading.
“Besides, microglia facilitate Aβ spreading.”
From Microglia in neurodegenerative diseases: mechanism and potential therapeutic targets (2023) · cites this paper as [154]
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“Our results are in line with studies showing that reduced microglial colocalization with β -amyloid is associated with a reduced β -amyloid burden (D ’ Errico et al., 2022; Spangenberg et al., 2019).”
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- Authors
- d’Errico, P., Ziegler-Waldkirch, S., Aires, V., Hoffmann, P., Mezö, C., Erny, D., Monasor, L. S., Liebscher, S., Ravi, V. M., Joseph, K., Schnell, O., Kierdorf, K., Staszewski, O., Tahirovic, S., Prinz, M., & Meyer-Luehmann, M.
- Affiliations
- University of Freiburg (DE)
- Munich Cluster for Systems Neurology (DE)
- ORCID
- Venue
- Nature Neuroscience
- Published
- 2021-11-22
- Volume
- 25
- Issue
- 1
- Pages
- 20-25
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- PMC
- PMC8737330
- OpenAlex
- W3217012249
- Cited by
- 214
- References
- 33
- Citations by year
- 2026: 31 · 2025: 59 · 2024: 43 · 2023: 35 · 2022: 44 · 2021: 2
- FWCI
- 19.48
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Neuroscience (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Open access LMU (Ludwid Maxmilian's Universitat Munchen) (submittedVersion, cc-by)
- DZNE Pub (submittedVersion, cc-by)
- Funders
- Alzheimer Forschung Initiative (18014, 18047)
- Deutsche Forschungsgemeinschaft (SFB-1160, SFB 992, ME3542/2‐1, EXC‐2189, SFB/ TRR 167, 390939984, TRR 167)
- Gottfried Wilhelm Leibniz Universität Hannover
- Roman, Marga und Mareille Sobek Stiftung
- Leibniz-Gemeinschaft
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Neurology › Intracerebral and Subarachnoid Hemorrhage Research
- Keywords
- microglia, amyloid-beta, microglial infiltration, amyloid plaques, neurodegeneration, in vivo imaging, microglial function
- MeSH terms
- Brain, Humans, Neurons, Amyloid beta-Peptides, Microglia, Plaque, Amyloid
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