The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease
Open accessAbstract
Alzheimer’s disease (AD) is associated with memory impairment and altered peripheral metabolism. Mounting evidence indicates that abnormal signaling in a brain-periphery metabolic axis plays a role in AD pathophysiology. The activation of pro-inflammatory pathways in the brain, including the interleukin-6 (IL-6) pathway, comprises a potential point of convergence between memory dysfunction and metabolic alterations in AD that remains to be better explored. Using T2-weighted magnetic resonance imaging (MRI), we observed signs of probable inflammation in the hypothalamus and in the hippocampus of AD patients when compared to cognitively healthy control subjects. Pathological examination of post-mortem AD hypothalamus revealed the presence of hyperphosphorylated tau and tangle-like structures, as well as parenchymal and vascular amyloid deposits surrounded by astrocytes. T2 hyperintensities on MRI positively correlated with plasma IL-6, and both correlated inversely with cognitive performance and hypothalamic/hippocampal volumes in AD patients. Increased IL-6 and suppressor of cytokine signaling 3 (SOCS3) were observed in post-mortem AD brains. Moreover, activation of the IL-6 pathway was observed in the hypothalamus and hippocampus of AD mice. Neutralization of IL-6 and inhibition of the signal transducer and activator of transcription 3 (STAT3) signaling in the brains of AD mouse models alleviated memory impairment and peripheral glucose intolerance, and normalized plasma IL-6 levels. Collectively, these results point to IL-6 as a link between cognitive impairment and peripheral metabolic alterations in AD. Targeting pro-inflammatory IL-6 signaling may be a strategy to alleviate memory impairment and metabolic alterations in the disease.
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Neuroinflammation in Alzheimer’s Disease: Current Progress in Molecular Signaling and Therapeutics
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Metadata
- Authors
- Lyra e Silva, N. M., Gonçalves, R. A., Pascoal, T. A., Lima-Filho, R. A. S., Resende, E. D. P. F., Vieira, E. L. M., Teixeira, A. L., de Souza, L. C., Peny, J. A., Fortuna, J. T. S., Furigo, I. C., Hashiguchi, D., Miya-Coreixas, V. S., Clarke, J. R., Abisambra, J. F., Longo, B. M., Donato, J., Fraser, P. E., Rosa-Neto, P., Caramelli, P., Ferreira, S. T., & De Felice, F. G.
- Venue
- Translational Psychiatry
- Published
- 2021-04-28
- Volume
- 11
- Issue
- 1
- Pages
- 251-251
- ISSN
- 2158-3188 (ISSN-L)
- OpenAlex
- W3158545443
- Cited by
- 347
- References
- 29
- FWCI
- 24.93
- Type
- journal article
- Language
- en
- Open access
- gold
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- CoChat. (2026). Citation check: Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease. https://app.cochat.ai/papers/10.1038/s41398-021-01349-z
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- Lyra e Silva, N. M., Gonçalves, R. A., Pascoal, T. A., Lima-Filho, R. A. S., Resende, E. D. P. F., Vieira, E. L. M., Teixeira, A. L., de Souza, L. C., Peny, J. A., Fortuna, J. T. S., Furigo, I. C., Hashiguchi, D., Miya-Coreixas, V. S., Clarke, J. R., Abisambra, J. F., Longo, B. M., Donato, J., Fraser, P. E., Rosa-Neto, P., . . . De Felice, F. G. (2021). Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease. Translational Psychiatry. https://doi.org/10.1038/s41398-021-01349-z
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
