Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals

Lombardi, Valter; Garcı́a, Magdalena; Rey, Luís; Cacabelos, Ramón

doi:10.1016/s0165-5728(99)00046-6

Cited by 172 publications

(92 citation statements)

References 41 publications

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“…A significant decrease of B and T cell percentages without changes of natural killer (NK) cells was previously reported (Richartz-Salzburger et al, 2007). These and other investigators also reported a slight increase in the percentage of CD4+ T cells and a decrease of CD8+ cells (Richartz-Salzburger et al, 2007;Lombardi et al, 1999). These data are not in complete agreement with other reports of no differences in the percentage and absolute number of CD3+ T cells, NK cells or CD4+ and CD8+ T cells (Speciale et al, 2007).…”

Section: Discussionmentioning

confidence: 46%

Immune profiling of Alzheimer patients

Pellicanò

Larbi

Goldeck

et al. 2012

Journal of Neuroimmunology

126

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Alzheimer's disease (AD) is characterized by extracellular senile plaques in the brain, containing amyloid-β peptide (Aβ). We identify immunological differences between AD patients and age-matched controls greater than those related to age itself. The biggest differences were in the CD4+ rather than the CD8+ T cell compartment resulting in lower proportions of naïve cells, more late-differentiated cells and higher percentages of activated CD4+CD25+ T cells without a Treg phenotype in AD patients. Changes to CD4+ cells might be the result of chronic stimulation by Aβ present in the blood. These findings have implications for diagnosis and understanding the aetiology of the disease.

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Section: Discussionmentioning

confidence: 46%

Immune profiling of Alzheimer patients

Pellicanò

Larbi

Goldeck

et al. 2012

Journal of Neuroimmunology

126

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“…PBMCs were isolated by Ficoll-Hypaque density gradient centrifugation and resuspended in RPMI 1640 medium supplemented with 10% fetal bovine serum, nonessential amino acids, 1 mM sodium pyruvate, 50 U/ml penicillin and 50 mg/ml streptomycin in 12 well plates at 10 6 cells/ml. Cells were cultured for 24 or 48 hours at 37 °C in 5% CO 2 in complete culture medium alone or stimulated with 2 μg/ml phytohemagglutinin (PHA) or 10 μg/ml lipopolysaccharide (LPS), concentrations and time points commonly used to optimally induce cytokine production (Arosio et al, 2004;Huberman et al, 1994;Lombardi et al, 1999). After incubation, samples were centrifuged and supernatants collected and stored at -70 °C until assayed.…”

Section: Cell Isolation and Culture Conditionsmentioning

confidence: 99%

Increased production of inflammatory cytokines in mild cognitive impairment

Magaki

Mueller

Dickson

et al. 2007

Experimental Gerontology

125

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Recent studies indicate that chronic inflammation plays a pathogenic role in both the central nervous system (CNS) and periphery in Alzheimer's disease (AD). We have screened for cytokines differentially produced by peripheral blood mononuclear cells (PBMCs) isolated from subjects with mild cognitive impairment (MCI) and mild AD subjects who had progressed from MCI using a commercially available cytokine array. Following determination of expressed cytokines, we quantified levels of the proinflammatory cytokines TNF-α, IL-6, and IL-8, and the antiinflammatory cytokine IL-10 using flow cytometry. We have found a significant increase in the levels of IL-6, IL-8, and IL-10 produced by PBMCs stimulated for 24 hours with phytohemagglutinin (PHA) in MCI subjects compared to healthy elderly controls. However, in PBMCs stimulated for 48 h with lipopolysaccharide (LPS), lower TNF-α/IL-10, IL-6/IL-10, and IL-8/IL-10 ratios were seen in MCI subjects. There were no differences in plasma levels of IL-8 between aged controls, MCI, and mild AD, and the levels of circulating IL-6 and IL-10 were below detection limits. Our data indicate that changes in cytokine production by PBMCs may be detected early in MCI, and an alteration of the immune response may precede clinical AD.

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“…Data for immunophenotypes were evaluated with the non-parametric Mann-Whitney U test since cell markers are known to have a non-Gaussian distribution (Lombardi et al, 1999). The flow cytometry data for APP and Aβ expression were analyzed by both comparing the percentage of cells of a certain population expressing the marker of interest and comparing the mean fluorescence units of each population.…”

Section: Statisticsmentioning

confidence: 99%

“…Furthermore, Shalit et al (1995)have demonstrated that in moderately severe, but not mild AD patients, there was a significant decrease in lymphocyte proliferation compared to controls. A decrease in proliferation in peripheral blood mononuclear cells (PBMCs) of AD patients has also been found (Lombardi et al, 1999). However, other reports indicate no differences in either CD4/CD8 ratios (Ikeda et al, 1991), total lymphocytes (Dysken et al, 1992) or the percentage of CD3+ lymphocytes (total T lymphocytes) (Lombardi et al,.…”

Section: Introductionmentioning

confidence: 99%

Immunophenotypes in the circulation of patients with mild cognitive impairment

Magaki

Yellon

Mueller

et al. 2008

Journal of Psychiatric Research

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Alterations in the peripheral immune system are associated with dementia and the neuropathology of Alzheimer's disease, but have yet to be studied early in the disease process. To test the hypothesis that the balance of immune cell phenotypes is disrupted in the early progression of memory deterioration, patients with mild cognitive impairment (MCI) and healthy elderly controls were examined for the distribution of subpopulations of leukocytes (lymphocytes, granulocytes, and monocytes) and lymphocyte subtypes (helper/inducer and suppressor/cytotoxic T lymphocytes and B lymphocytes) in blood. MCI subjects had a significantly higher percentage of total lymphocytes and a lower percentage of granulocytes compared to elderly controls. Furthermore, the expression of cell surface amyloid precursor protein (APP) and intracellular amyloid-β peptide (Aβ) in lymphocytes and monocytes were determined. We found lymphocyte APP expression to be significantly increased in MCI subjects compared to controls. Our data indicate that changes in immunological parameters may be detected early in MCI, and an alteration of the immune response may precede clinical AD.

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Characterization of cytokine production, screening of lymphocyte subset patterns and in vitro apoptosis in healthy and Alzheimer's Disease (AD) individuals

Cited by 172 publications

References 41 publications

Immune profiling of Alzheimer patients

Immune profiling of Alzheimer patients

Increased production of inflammatory cytokines in mild cognitive impairment

Immunophenotypes in the circulation of patients with mild cognitive impairment

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