Dataset Information

Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?

ABSTRACT:

Background

Although the mechanisms underlying AD neurodegeneration are not fully understood, it is now recognised that inflammation could play a crucial role in the initiation and progression of AD neurodegeneration. A neuro-inflammatory network, based on the anomalous activation of microglial cells, includes the production of a number of inflammatory cytokines both locally and systemically. These may serve as diagnostic markers or therapeutic targets for AD neurodegeneration.

Methods

We have measured the levels of the inflammation-related cytokines and receptors of the IL-1 family in serum of subjects with AD, compared to mild cognitive impairment (MCI), subjective memory complaints (SMC), and normal healthy subjects (NHS). Using a custom-made multiplex ELISA array, we examined ten factors of the IL-1 family, the inflammation-related cytokines IL-1?, IL-1?, IL-18, and IL-33, the natural inhibitors IL-1Ra and IL-18BP, and the soluble receptors sIL-1R1, sIL-1R2, sIL-1R3, and sIL-1R4.

Results

The inflammatory cytokines IL-1? and IL-1?, their antagonist IL-1Ra, and their soluble receptor sIL-1R1 were increased in AD. The decoy IL-1 receptor sIL-1R2 was only increased in MCI. IL-33 and its soluble receptor sIL-1R4 were also significantly higher in AD. The soluble form of the accessory receptor for both IL-1 and IL-33 receptor complexes, sIL-1R3, was increased in SMC and even more in AD. Total IL-18 levels were unchanged, whereas the inhibitor IL-18BP was significantly reduced in MCI and SMC, and highly increased in AD. The levels of free IL-18 were significantly higher in MCI.

Conclusions

AD is characterised by a significant alteration in the circulating levels of the cytokines and receptors of the IL-1 family. The elevation of sIL-1R4 in AD is in agreement with findings in other diseases and can be considered a marker of ongoing inflammation. Increased levels of IL-1Ra, sIL-1R1, sIL-1R4, and IL-18BP distinguished AD from MCI and SMC, and from other inflammatory diseases. Importantly, sIL-1R1, sIL-1R3, sIL-1R4, and IL-18BP negatively correlated with cognitive impairment. A significant elevation of circulating sIL-1R2 and free IL-18, not present in SMC, is characteristic of MCI and disappears in AD, making them additional interesting markers for evaluating progression from MCI to AD.

SUBMITTER: Italiani P

PROVIDER: S-EPMC6292179 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Publications

Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?

Italiani Paola P Puxeddu Ilaria I Napoletano Sabrina S Scala Emanuele E Melillo Daniela D Manocchio Simone S Angiolillo Antonella A Migliorini Paola P Boraschi Diana D Vitale Emilia E Di Costanzo Alfonso A

Journal of neuroinflammation 20181212 1

<h4>Background</h4>Although the mechanisms underlying AD neurodegeneration are not fully understood, it is now recognised that inflammation could play a crucial role in the initiation and progression of AD neurodegeneration. A neuro-inflammatory network, based on the anomalous activation of microglial cells, includes the production of a number of inflammatory cytokines both locally and systemically. These may serve as diagnostic markers or therapeutic targets for AD neurodegeneration.<h4>Methods ...[more]

PMID: 30541566

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Dataset Information

Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?

Background

Methods

Results

Conclusions

Publications

Circulating levels of IL-1 family cytokines and receptors in Alzheimer's disease: new markers of disease progression?

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