T Cells Specifically Targeted to Amyloid Plaques Enhance Plaque Clearance in a Mouse Model of Alzheimer's Disease
Open accessAbstract
Patients with Alzheimer's disease (AD) exhibit substantial accumulation of amyloid-beta (Abeta) plaques in the brain. Here, we examine whether Abeta vaccination can facilitate the migration of T lymphocytes to specifically target Abeta plaques and consequently enhance their removal. Using a new mouse model of AD, we show that immunization with Abeta, but not with the encephalitogenic proteolipid protein (PLP), results in the accumulation of T cells at Abeta plaques in the brain. Although both Abeta-reactive and PLP-reactive T cells have a similar phenotype of Th1 cells secreting primarily IFN-gamma, the encephalitogenic T cells penetrated the spinal cord and caused experimental autoimmune encephalomyelitis (EAE), whereas Abeta T cells accumulated primarily at Abeta plaques in the brain but not the spinal cord and induced almost complete clearance of Abeta. Furthermore, while a single vaccination with Abeta resulted in upregulation of the phagocytic markers triggering receptors expressed on myeloid cells-2 (TREM2) and signal regulatory protein-beta1 (SIRPbeta1) in the brain, it caused downregulation of the proinflammatory cytokines TNF-alpha and IL-6. We thus suggest that Abeta deposits in the hippocampus area prioritize the targeting of Abeta-reactive but not PLP-reactive T cells upon vaccination. The stimulation of Abeta-reactive T cells at sites of Abeta plaques resulted in IFN-gamma-induced chemotaxis of leukocytes and therapeutic clearance of Abeta.
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Recruitment of adaptive immune cells, particularly T and B lymphocytes, can exacerbate neurodegeneration through sustained cytokine production.
“In parallel, recruitment of adaptive immune cells—particularly T and B lymphocytes—can further exacerbate neurodegeneration through sustained cytokine production despite their initial roles in aggregate clearance [37–41].”
From Targeted Nanoparticles for Drug Delivery Across the Blood–Brain Barrier in Early and Late Stages of Alzheimer's Disease: A Review (2026) · cites this paper as [38]
The Discussion (page not provided) says Aβ-reactive B and T cells are potentially pathogenic, citing risks including a strong proinflammatory cytokine profile in CD4 T cells. It does not establish that sustained cytokine production by recruited T and B cells exacerbates neurodegeneration. In this mouse model, the Results instead report reduced IL-6 and TNF-α alongside enhanced plaque clearance. (LLM, conf=0.86)
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- Authors
- Fisher, Y., Nemirovsky, A., Baron, R., & Monsonego, A.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Corresponding author
- Monsonego, Alon
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2010-05-26
- Volume
- 5
- Issue
- 5
- Pages
- e10830
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2877087
- OpenAlex
- W2052316972
- Cited by
- 83
- References
- 64
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 10 · 2023: 3 · 2022: 1 · 2021: 6 · 2020: 6 · 2019: 4 · 2018: 8 · 2017: 4 · 2016: 1 · 2015: 9 · 2014: 6 · 2013: 12 · 2012: 3
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Israel Science Foundation
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid plaques, T cell migration, plaque clearance, Th1 cells, interferon-gamma, experimental autoimmune encephalomyelitis, proteolipid protein, TREM2, TNF-α, interleukin-6, hippocampus, chemotaxis
- MeSH terms
- Alzheimer Disease, Amyloid, Animals, Brain, Cell Movement, Disease Models, Animal, Immunization, Interferon-gamma, Mice, Inbred C57BL, Mice, Transgenic, T-Lymphocytes, CD4-Positive T-Lymphocytes, Amyloid beta-Peptides, CD8-Positive T-Lymphocytes, Myelin Proteolipid Protein, Mice, Plaque, Amyloid
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