The DOI matches its Crossref record; 273 of the 273 references it cites were found in a registry or an index.
Microglial phagocytosis in Alzheimer disease
Abstract
Accumulating evidence indicates that Alzheimer disease (AD) is caused by dysregulated microglial phagocytosis. The main risk factor for AD is age, and ageing reduces microglial phagocytosis of amyloid-β (Aβ) plaques, while increasing microglial phagocytosis of synapses and neurons. Most of the known genetic risk for AD can be linked to microglial phagocytosis, including ABCA1, ABI3, ACE, ADAM17, APOE, APP, BIN1, BLNK, CD2AP, CD33, CLU, CR1, CTSB, CTSH, EED, GRN, INPP5D, LILRB2, PICALM, PLCG2, PSEN1, PTK2B, SIGLEC11, SORL1, SPI1, TMEM106B and TREM2. Moreover, the only disease-modifying treatments for AD - anti-Aβ antibodies - work by increasing microglial phagocytosis of Aβ aggregates. Microglial phagocytosis of Aβ via TREM2, LRP1, CD33, TAM receptors and anti-Aβ antibodies appears to reduce AD pathology by pruning and compacting plaques, restricting subsequent tau pathology, whereas microglial phagocytosis of synapses and neurons seems detrimental in the later stages of AD, via complement, P2Y 6 receptor and TREM2. However, the roles of microglial phagocytosis in AD are complex and multifaceted, and improved treatments are likely to require a deeper understanding of these roles.
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Metadata
- Authors
- Brown, G. C., St George-Hyslop, P., Paolicelli, R. C., & Lemke, G.
- Affiliations
- University of Cambridge (GB)
- University of Lausanne (CH)
- Salk Institute for Biological Studies (US)
- Corresponding author
- Brown, Guy C.
- Venue
- Nature Reviews Neurology
- Published
- 2025-11-28
- Volume
- 22
- Issue
- 1
- Pages
- 54-69
- ISSN
- 1759-4758 (ISSN-L)
- 1759-4766
- OpenAlex
- W4416789883
- Semantic Scholar
- 78f3fc40eab69f8c43be0f3bc2dae0bf53ba65f5
- Cited by
- 36
- References
- 272
- Citations by year
- 2026: 36
- FWCI
- 3.48
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature Reviews Neurology (publishedVersion)
- PubMed (publishedVersion)
- IRIS (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Immunology and Microbiology › Immunology › Phagocytosis and Immune Regulation
- Keywords
- Alzheimer's disease, microglial phagocytosis, amyloid plaques, TREM2, anti-amyloid antibodies, synaptic pruning, neurodegeneration, genetic risk factors, complement system, P2Y6 receptor, LRP1, CD33, TAM receptors, tau pathology, disease-modifying therapy
- MeSH terms
- Alzheimer Disease, Animals, Humans, Phagocytosis, Amyloid beta-Peptides, Microglia
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