Cited by 36Neuroinflammation and Neurodegeneration MechanismsAlzheimer's disease research and treatmentsPhagocytosis and Immune Regulation

Microglial phagocytosis in Alzheimer disease

Brown, Guy C., St George-Hyslop, Peter, Paolicelli, Rosa C., Lemke, Greg·2026·Nature Reviews Neurology

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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Crossref · 10.1038/s41582-025-01162-y

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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
Cited by
36
References
273
Citations by year
2026: 36
FWCI
3.48
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Reviews Neurology (publishedVersion)
  • PubMed (publishedVersion)
  • IRIS (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Physiology › 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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