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Wild‐type sTREM2 blocks Aβ aggregation and neurotoxicity, but the Alzheimer's R47H mutant increases Aβ aggregation
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sTREM2 has been shown to prevent Aβ aggregation and promote phagocytosis.
“sTREM2 has been shown to prevent Aβ aggregation and promote phagocytosis. 20 , 38 , 39”
From Inhibition of Acyl‐CoenzymeA: Cholesterol Acyltransferase 1 promotes shedding of soluble triggering receptor on myeloid cells 2 (TREM2) and low‐density lipoprotein receptor 1 (LRP1)‐dependent phagocytosis of amyloid beta protein in microglia (2025) · cites this paper as [20]
The Discussion (page unavailable) reports that wild-type sTREM2 inhibits Aβ fibril and larger-oligomer formation, supporting the aggregation part of the claim. Our copy does not report that sTREM2 promotes phagocytosis; the only exact mention of phagocytosis is in a cited reference about microglial phagocytosis of neurons. (LLM, conf=0.88)
Experimental — accuracy not yet measuredsTREM2 binds Aβ, preventing its aggregation and increasing clearance.
“Multiple studies have reported that sTREM2 binds Aβ, preventing its aggregation and increasing clearance. 18 , 19 , 20”
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Citations
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MethodTREM2 Variants in Alzheimer's Disease
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Humanized TREM2 mice reveal microglia-intrinsic and -extrinsic effects of R47H polymorphism
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Cited by
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“TREM2 is also present as a soluble protein (sTREM2), and most studies have focused on sTREM2 as a potential biomarker for AD progression [19–26], while very few studies have explored sTREM2 biological functions [30, 31, 49, 50].”
BackgroundMicroglial phagocytosis in Alzheimer disease
Brown, G. C., St George-Hyslop, P., Paolicelli, R. C., & Lemke, G. (2026) · Nature Reviews Neurology · doi:10.1038/s41582-025-01162-y · Cited by 36
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Cancer Hacks Neurodegeneration: Cystatin-C as a Bridge for Microglial Amyloid Clearance via TREM2
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Self-citation
Metadata
- Authors
- Vilalta, A., Zhou, Y., Sevalle, J., Griffin, J. K., Satoh, K., Allendorf, D. H., De, S., Puigdellívol, M., Bruzas, A., Burguillos, M. A., Dodd, R. B., Chen, F., Zhang, Y., Flagmeier, P., Needham, L.-M., Enomoto, M., Qamar, S., Henderson, J., Walter, J., Fraser, P. E., Klenerman, D., Lee, S. F., St George-Hyslop, P., & Brown, G. C.
- ORCID
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 296
- Pages
- 100631
- ISSN
- 0021-9258
- PMC
- PMC8113883
- Cited by
- 77
- References
- 15
- Language
- en
- Licence
- Funders
- Innovative Medicines Initiative
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