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Mouse Footpad Inoculation Model to Study Viral-Induced Neuroinflammatory Responses
Published on: June 14, 2020
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Basic Science and Pathogenesis
Cassandra O Blew1, Michael R Duggan1, Dimitrios Tsitsipatis2
1Laboratory of Behavioral Neuroscience, National Institute on Aging, Intramural Research Program, Baltimore, MD, USA.
Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
Summary
Growth/differentiation factor-15 (GDF15) may increase dementia risk by altering macrophage functions. This protein influences key pathways, including interferon signaling and pyruvate metabolism, potentially contributing to dementia development.
Area of Science:
- Neuroscience
- Immunology
- Metabolomics
Background:
- Elevated growth/differentiation factor-15 (GDF15) in plasma is linked to dementia development.
- The precise role and biological mechanisms of GDF15 in dementia risk remain unclear.
Purpose of the Study:
- To investigate the biological mechanisms by which GDF15 influences dementia incidence.
- To determine if GDF15 is a valid risk factor for dementia.
Main Methods:
- Macrophage proteomic changes were analyzed after exposure to recombinant human GDF15 (rhGDF15).
- Pathway enrichment analyses identified biological pathways affected by rhGDF15.
- These pathways were recreated in large cohorts (ARIC study) to assess associations with dementia risk.
Main Results:
- rhGDF15 exposure upregulated metabolic pathways and downregulated inflammatory responses in macrophages.
- 31 and 14 pathway composite scores were associated with midlife and late-life dementia risk, respectively.
- Interferon signaling, pyruvate metabolism, and heme scavenging were key mediators linking GDF15 to dementia risk.
Conclusions:
- GDF15's association with dementia risk is potentially mediated by its effects on macrophages and myeloid cells.
- GDF15 may increase dementia risk by attenuating interferon signaling and heme scavenging while increasing pyruvate metabolism.
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