When less is more and when it isn’t: Microglial Spi1 and the limits of what we know
Abstract
Microglia are key players in Alzheimer's disease, but the transcriptional control of their phagocytic function remains unclear. Kim et al. show that mouse microglial Spi1 deletion worsens amyloid pathology by impairing Aβ clearance through Syk, Lyn, and Fcgr1, providing new insight into PU.1-dependent regulatory networks and microglial functions in neurodegeneration.
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A common haplotype lowers PU.1 expression in myeloid cells and delays onset of Alzheimer's disease
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Kim, B., Tate, M. D., Karahan, H., Wijeratne, H. R. S., Sharify, A. D., Wang, S. S., Kim, J. R., Al-Amin, M. M., Hartigan, K., Chung, S., et al. (2026) · Neuron · doi:10.1016/j.neuron.2026.03.011 · Cited by 6 · see citing works
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- Authors
- Koldamova, R., Fitz, N. F., & Lefterov, I.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Koldamova, Radosveta
- Lefterov, Iliya
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2026-08
- Volume
- 114
- Issue
- 15
- Pages
- 2669-2671
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W7172514298
- Semantic Scholar
- 730071b9bddc95d154aa66180e3971bb25f9b696
- Cited by
- 0
- References
- 10
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH
- 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
- microglia, PU.1, Alzheimer's disease, amyloid-beta clearance, Syk, Lyn kinase, phagocytosis, transcriptional regulation, neurodegeneration, amyloid pathology
- MeSH terms
- Proto-Oncogene Protein Spi-1, Alzheimer Disease, Animals, Humans, Proto-Oncogene Proteins, Trans-Activators, Amyloid beta-Peptides, Microglia, Mice
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