Granulocyte-macrophage colony-stimulating factor neuroprotective activities in Alzheimer’s disease mice
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We investigated the effects of granulocyte-macrophage colony stimulating factor (GM-CSF) on behavioral and pathological outcomes in Alzheimer's disease (AD) and non-transgenic mice. GM-CSF treatment in AD mice reduced brain amyloidosis, increased plasma Aβ, and rescued cognitive impairment with increased hippocampal expression of calbindin and synaptophysin and increased levels of doublecortin-positive cells in the dentate gyrus. These data extend GM-CSF pleiotropic neuroprotection mechanisms in AD and include regulatory T cell-mediated immunomodulation of microglial function, Aβ clearance, maintenance of synaptic integrity, and induction of neurogenesis. Together these data support further development of GM-CSF as a neuroprotective agent for AD.
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The levels of antiageing factors such as GDF11, TIMP2 and CSF2 are reduced; these factors are linked to improved microglial phagocytosis and neurogenesis and reduce the amyloid-β load, thus enhancing cognition.
“In contrast, the levels of antiageing factors, such as GDF11, tissue inhibitor of metalloproteinase 2 (TIMP2) and granulocyte‒macrophage colony stimulating factor (CSF2), are reduced. These factors are linked to improved microglial phagocytosis and neurogenesis and reduce the Aβ load, thus enhancing cognition.72,322–324”
From Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances (2025) · cites this paper as [324]
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Synaptic degeneration in Alzheimer disease
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Adoptive therapy with amyloid-β specific regulatory T cells alleviates Alzheimer's disease
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Amyloid-β specific regulatory T cells attenuate Alzheimer’s disease pathobiology in APP/PS1 mice
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Self-citationTherapeutic anti‐amyloid β antibodies cause neuronal disturbances
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Self-citationPeripheral sTREM2-Related Inflammatory Activity Alterations in Early-Stage Alzheimer’s Disease
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A myeloid trisomy 21-associated gene variant is protective from Alzheimer’s disease
Jin, M., Ma, Z., Dang, R., Zhang, H., Kim, R., Xue, H., Pascual, J. R., Yu, H., Papetti, A. V., Liú, Y., et al. (2025) · Nature Neuroscience · doi:10.1038/s41593-025-02117-8 · Cited by 9 · see citing works
Combination Therapy for Alzheimer's Disease: Perspectives of the EU/US CTAD Task Force
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Neuroprotective Immunity for Neurodegenerative and Neuroinfectious Diseases
Olson, K. E., Mosley, R. L., & Gendelman, H. E. (2020) · Springer eBooks · doi:10.1007/978-3-030-33946-3_8 · Cited by 2 · see citing works
Self-citationGrowth factors and their receptors
Lazaldin, M. A. M., Lambuk, L., Ahmad, S., & Mohamud, R. (2023) · Elsevier eBooks · doi:10.1016/b978-0-443-18677-6.00005-1 · Cited by 1 · see citing works
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Reevaluation of EPO and its Derivatives Centering on β Common ReceptorPreprint
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Self-citationCan we refute a role for infections in Alzheimer's disease pathogenesis?
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- Authors
- Kiyota, T., Machhi, J., Lu, Y., Dyavarshetty, B., Nemati, M., Yokoyama, I., Mosley, R. L., & Gendelman, H. E.
- Affiliations
- University of Nebraska Medical Center (US)
- Corresponding author
- Gendelman, Howard E.
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2018-06
- Volume
- 319
- Pages
- 80-92
- ISSN
- 0165-5728 (ISSN-L)
- PMC
- PMC5916331
- OpenAlex
- W2791554250
- Cited by
- 80
- References
- 120
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 14 · 2023: 13 · 2022: 12 · 2021: 11 · 2020: 12 · 2019: 4 · 2018: 1
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (am, 324 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Journal of Neuroimmunology (acceptedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (NS036126, AG043540, MH062261, NS034239, NS043985, DA028555, MH064570)
- U.S. Department of Defense (421, 20-09A, 421\u201320-09 A)
- 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
- GM-CSF, Alzheimer's disease, neuroprotection, amyloid-beta, cerebral amyloidosis, cognitive impairment, hippocampus, synaptophysin, calbindin, doublecortin, dentate gyrus neurogenesis, microglial function, regulatory T cells, immunomodulation, synaptic integrity
- MeSH terms
- Alzheimer Disease, Animals, Brain, Mice, Transgenic, Granulocyte-Macrophage Colony-Stimulating Factor, Neuroprotective Agents, Mice
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