Intrathecal levels of IL-6, IL-11 and LIF in Alzheimer's disease and frontotemporal lobar degeneration

Galimberti, Daniela; Venturelli, Eliana; Fenoglio, Chiara; Guidi, Ilaria; Clara, Villa; Bergamaschini, Luigi; Cortini, Francesca; Scalabrini, D.; Baron, Pierluigi; Vergani, Carlo; Bresolin, Nereo; Scarpini, Elio

doi:10.1007/s00415-008-0737-6

Cited by 77 publications

(66 citation statements)

References 35 publications

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“…1A, B). There was no statistically signifi cant difference in LXA 4 or RvD1 levels between DMSO and A ␤ 40 conditions (supplementary Fig. 2A, B).…”

Section: Lms Released By Pbmcsmentioning

confidence: 91%

“…LXA 4 and RvD1 levels. Upon A ␤ 40 exposure, the release of LXA 4 and RvD1 from PBMCs was reduced after 6 months in the placebo supplementation group compared with baseline, while in the n-3 FA supplementation group the levels remained similar to that observed at baseline ( Fig.…”

Section: Lms Released By Pbmcsmentioning

confidence: 97%

“…2A, B). 4 ratio. In the supernatant of vehicle-treated cells, the ratio between LXA 4 and LTB 4 was not altered after 6 months of treatment with n-3 FAs or placebo (supplementary Fig.…”

Section: Lms Released By Pbmcsmentioning

confidence: 99%

“…Recent studies have indicated that resolution of infl ammation is disturbed in AD ( 12,13 ) and AD-related models (14)(15)(16). Treatment with one of the SPMs, lipoxin A 4 (LXA 4 ), has been demonstrated to rescue synaptic loss and reduce AD-like pathologies in transgenic AD mouse models ( 17,18 ). These studies suggest that stimulating resolution of infl am mation with SPMs is a promising new strategy for AD therapy.…”

Section: Pbmc Preparation and Ex Vivo Experimentsmentioning

confidence: 99%

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Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Wang

Hjorth

Vedin

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org Many diseases of the brain display signs of infl ammation, including Alzheimer's disease (AD), the most common type of dementia. The association between infl ammation and AD is evidenced from many different disciplines of research. Postmortem studies have revealed increased levels of proinfl ammatory cytokines in the AD brain ( 1-3 ), particularly around the amyloid plaques, and further support is provided by analysis of clinical samples from AD patients, including elevated proinfl ammatory markers in cerebrospinal fl uid (CSF) ( 4 ) and plasma/serum ( 5-7 ) samples. Epidemiological studies have shown that longterm use of nonsteroidal anti-infl ammatory drugs (NSAIDs) confers reduced prevalence of AD ( 8 ). However, prospective clinical trials based on NSAIDs have not been successful in reducing the cognitive decline in AD ( 8, 9 ).Consumption of PUFAs, especially the n-3 FAs DHA and EPA, is well known for benefi cial effects in the regulation of infl ammation ( 10 ). PUFAs can modulate the infl ammatory response by changing cell membrane fl uidity and composition, leading to effects on the function of receptors, and the conductance of ion channels involved in immune activation. In recent years, the concept of resolution of infl ammation has received attention due to the discovery of specialized proresolving mediators (SPMs). SPMs are lipid mediators (LMs) derived from PUFAs and play a key role in resolution, in which the tissue is restored by removal of cellular and molecular debris, and regeneration/ Abstract Specialized proresolving mediators (SPMs) induce resolution of infl ammation. SPMs are derivatives of n-3 and n-6 PUFAs and may mediate their benefi cial effects. It is unknown whether supplementation with PUFAs infl uences the production of SPMs. Alzheimer's disease (AD) is associated with brain infl ammation and reduced levels of SPMs. The OmegAD study is a randomized, double-blind, and placebo-controlled clinical trial on AD patients, in which placebo or a supplement of 1.7 g DHA and 0.6 g EPA was taken daily for 6 months. Plasma levels of arachidonic acid decreased, and DHA and EPA levels increased after 6 months of n-3 FA treatment. Peripheral blood mononuclear cells (PBMCs) were obtained before and after the trial. Analysis of the culture medium of PBMCs incubated with amyloid-␤ 1-40 showed unchanged levels of the SPMs lipoxin A 4 and resolvin D1 in the group supplemented with n-3 FAs, whereas a decrease was seen in the placebo group. The changes in SPMs showed correspondence to cognitive changes. Changes in the levels of SPMs were positively correlated to changes in transthyretin. We conclude that supplementation with n-3 PUFAs for 6 months prevented a reduction in SPMs released from PBMCs of AD patients, which was associated with changes in cognitive function.

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“…1A, B). There was no statistically signifi cant difference in LXA 4 or RvD1 levels between DMSO and A ␤ 40 conditions (supplementary Fig. 2A, B).…”

Section: Lms Released By Pbmcsmentioning

confidence: 91%

Section: Lms Released By Pbmcsmentioning

confidence: 97%

“…2A, B). 4 ratio. In the supernatant of vehicle-treated cells, the ratio between LXA 4 and LTB 4 was not altered after 6 months of treatment with n-3 FAs or placebo (supplementary Fig.…”

Section: Lms Released By Pbmcsmentioning

confidence: 99%

Section: Pbmc Preparation and Ex Vivo Experimentsmentioning

confidence: 99%

See 2 more Smart Citations

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Wang

Hjorth

Vedin

et al. 2015

Journal of Lipid Research

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show abstract

“…

In a recent study, Galimberti et al [2] reported a significant increase of IL-11 disease (AD n = 43) and frontotomporal lobar degeneration (FTLD n = 24) in patients with Alzheimer's disease in comparison to age-matched controls (n = 30). At the same time, IL-6 showed only a non-significant increase in demented subjects.

…”

mentioning

confidence: 97%

Intrathecal levels of IL-6 in Alzheimer’s disease

Jellinger¹

2009

J Neurol

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In a recent study, Galimberti et al. [2] reported a significant increase of IL-11 disease (AD n = 43) and frontotomporal lobar degeneration (FTLD n = 24) in patients with Alzheimer's disease in comparison to age-matched controls (n = 30). At the same time, IL-6 showed only a non-significant increase in demented subjects. Measurement of CSF IL-6 levels in AD have revealed contradictory results-unchanged [3,5] and increased [1,8,9]. In our personal studies in a cohort of 169 aged subjects, we found probable AD (n = 27), non-AD dementia (n = 24, including FTLD n = 10 and vascular dementia n = 5), and other CNS disorders without cognitive impairment (infections, vascular, neurodegenerative diseases n = 69). A specific immunoabsorbent assay (ELISA, R&D Systems, Minneapolis, MN, USA) revealed a significant increase of IL-6 immunoreactivity in CSF of both AD and non-AD dementias compared to controls (P \ 0.03), despite broad overlap. AD patients with late onset ([65 years) had significantly higher values than those with early onset (P \ 0.05), but, as in Galimberti's cohort, there were no correlations of CSF IL-6 with age, MMSE scores, disease duration, or CSF Ab-42 and T-tau [4,6]. These data and increased CSL IL-6 levels in hypertensive encephalopathy [7] suggest that it may reflect IL-mediated immunologic phenomena in the course of neurodegenerative processes.

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Finding a pathological diagnosis for Alzheimer's disease: Are inflammatory molecules the answer?

Bhamra

Ashton

2012

Electrophoresis

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Conventional diagnostic tools for Alzheimer's disease (AD) are currently based on a number of clinical criteria, and a definitive diagnosis still relies on pathological evaluation at autopsy. Moreover, neurodegenerative changes are believed to begin years before clinical presentation. There is therefore an essential need for a reliable AD biomarker to aid in the identification of preclinical disease, early diagnosis, prediction of disease progression and treatment response. There is mounting evidence that chronic inflammatory processes play a fundamental role in the progression of neuropathological changes in AD. Clinical and experimental evidence supports the involvement of inflammatory changes in the early stages of AD, even before the appearance of amyloid deposits. Therefore biomarkers that reflect the inflammatory process in AD hold promise. Tests based on these should preferably be reliable, noninvasive and costeffective, which has led to an increasing focus on the use of blood-based biomarkers. This review considers the current progress in AD inflammatory biomarker research followed by a detailed analysis of two leading putative inflammatory biomarkers: α-2-macroglobulin and clusterin.

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Intrathecal levels of IL-6, IL-11 and LIF in Alzheimer's disease and frontotemporal lobar degeneration

Cited by 77 publications

References 35 publications

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Effects of n-3 FA supplementation on the release of proresolving lipid mediators by blood mononuclear cells: the OmegAD study

Intrathecal levels of IL-6 in Alzheimer’s disease

Finding a pathological diagnosis for Alzheimer's disease: Are inflammatory molecules the answer?

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