Immune system‐associated antigens on the surface of peripheral blood lymphocytes in patients with Alzheimer's disease

Ikeda, Takuo; Yamamoto, Kiyoshi; Takahashi, K.; Yamada, Michio

doi:10.1111/j.1600-0447.1991.tb05573.x

Cited by 31 publications

(19 citation statements)

References 19 publications

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“…Moreover, although MCI subjects had a slightly lower proportion of CD4+ cells, we saw no differences in the percentage of CD8+ cells and the ratio of CD4+/CD8+ cells between MCI and controls. These results are in agreement with other investigators who have found no differences in the distribution of CD4+ and CD8+ cells and CD4+/CD8+ ratios in AD patients compared to controls (Richartz-Salzburger et al, 2006;Ikeda et al, 1991).…”

Section: Discussionsupporting

confidence: 94%

“…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,. 1999) between AD and controls.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 94%

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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“…Nevertheless, although some immunologi cal components have been associated with the neuropathological alterations of AD [1][2][3][4][5][6][7][8], a conclusive in volvement of immunity in the pathogenesis of the disease is still under debate [34], Immune reactions in the periph eral blood may be expected to occur in brain regions of AD patients and particularly IL-2 and the appearance of IL-2 receptor may induce activation of a cascade reaction of immunity determining T cell and NK cell proliferation in the brain of subjects suffering from AD [5,35]. More over, activated lymphocytes can penetrate the bloodbrain barrier so inducing possible neuroimmunological changes in the brain parenchyma [6,36].…”

Section: Resultsmentioning

confidence: 99%

Enhanced Cytotoxic Response of Natural Killer Cells to lnterleukin-2 in Alzheimer's Disease

Solerte

Fioravanti²,

Severgnini³

et al. 1996

Dement Geriatr Cogn Disord

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Experimental data suggest an involvement of immune cellular components in the development of Alzheimer''s disease (AD). Against this background, the spontaneous natural killer (NK) cell activity and the NK-induced cytotoxicity after interleukin-2 (IL-2) were studied in healthy elderly subjects and in patients with dementia of Alzheimer type (SDAT) and multi-infarct type (MID). Higher NK cytotoxicity (expressed as total lysis and percent increase) at different IL-2 concentrations (50 and 100 IU/ml/cells) was demonstrated in patients with SDAT than in healthy elderly subjects (p < 0.001) and MID patients (p < 0.001). NK cell activity of MID patients was similar to that of healthy elderly and healthy young subjects. A negative correlation between the percent increase in NK cytotoxicity after IL-2 and the Mini Mental State Examination Score was also found in SDAT patients (p < 0.01). Alterations of IL-2-mediated NK cytotoxicity may therefore support the neuroimmune hypothesis of AD.

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“…Specifically, it has been shown that peripheral T lymphocytes isolated from AD patients demonstrate decreased amounts of the CD45R isoform compared with age-matched nondemented control subjects (Ikeda et al, 1991). To examine whether increasing CD45 activity could block microglial activation resulting from co-treatment with phen and A␤, we activated wild-type microglia with phen and A␤, added CD45 recombinant protein (20 U/ml) to these cells, and measured NO and TNF-␣ release.…”

Section: Discussionmentioning

confidence: 99%

CD45 Opposes β-Amyloid Peptide-Induced Microglial Activation via Inhibition of p44/42 Mitogen-Activated Protein Kinase

et al. 2000

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Reactive microglia have been suggested to play a role in the Alzheimer's disease (AD) process, and previous studies have shown that expression of CD45, a membrane-bound proteintyrosine phosphatase (PTP), is elevated in microglia in AD brain compared with controls. To investigate the possible role of CD45 in microglial responsiveness to ␤-amyloid (A␤) peptides, we first co-treated primary cultured microglia with a tyrosine phosphatase inhibitor [potassium bisperoxo (1,10-phenanthroline) oxovanadate (phen), 5 M] and freshly solubilized A␤ peptides (1000 nM). Data show synergistic induction of microglial activation as evidenced by tumor necrosis factor ␣ (TNF-␣) production and nitric oxide (NO) release, both of which we show to be dependent on activation of p44/42 mitogen-activated protein kinase (MAPK). Furthermore, co-treatment with phen and A␤ peptides results in microglia-induced neuronal cell injury. Stimulation of microglial CD45 by anti-CD45 antibody markedly inhibits these effects via inhibition of p44/42 MAPK, suggesting that CD45 is a negative regulator of microglial activation. Accordingly, primary cultured microglia from CD45-deficient mice demonstrate hyper-responsiveness to A␤, as evidenced by TNF-␣ release, NO production, and neuronal injury after stimulation with A␤ peptides. As a validation of these findings in vivo, brains from a transgenic mouse model of AD [transgenic Swedish APPoverexpressing (Tg APP sw ) mice] deficient for CD45 demonstrate markedly increased production of TNF-␣ compared with Tg APP sw mice. Taken together, these results suggest that therapeutic agents that stimulate the CD45 PTP signaling pathway may be effective in suppressing microglial activation associated with AD. Key words: Alzheimer's disease; ␤-amyloid; microlgia; neurons; mitogen-activated protein kinase; CD45; protein-tyrosine phosphatase; tyrosine phospatase inhibitor; TNF-␣; nitric oxideIt has been suggested that activated microglia play a key role in the inflammatory processes of neurodegenerative diseases such as Alzheimer's disease (AD), because reactive microglia secrete cytokines, including tumor necrosis factor ␣ (TNF-␣) and interleukin-1␤, which promote neurodegeneration (Meda et al., 1995;Rogers et al., 1996;Barger and Harmon, 1997). However, current antiinflammatory therapeutics directed against AD, such as nonsteroidal anti-inflammatory drugs (NSAIDs), only partially suppress microglial activation (Mackenzie and Munoz, 1998) and, therefore, may not provide the greatest therapeutic benefits for AD. This suggestion is supported by clinical evidence, in which elderly persons using NSAIDs demonstrate only an ϳ20% reduction in risk for AD (Beard et al., 1998), and AD patients using NSAIDs have only partial amelioration of disease symptoms (Rich et al., 1995). Thus, a more viable therapeutic strategy may be combination of NSAIDs with specific inhibitors of microglial activation.Most of our knowledge concerning the molecular mediators of microglial activation comes from studies involving peripheral lymphocytes....

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Immune system‐associated antigens on the surface of peripheral blood lymphocytes in patients with Alzheimer's disease

Cited by 31 publications

References 19 publications

Immunophenotypes in the circulation of patients with mild cognitive impairment

Immunophenotypes in the circulation of patients with mild cognitive impairment

Enhanced Cytotoxic Response of Natural Killer Cells to lnterleukin-2 in Alzheimer's Disease

CD45 Opposes β-Amyloid Peptide-Induced Microglial Activation via Inhibition of p44/42 Mitogen-Activated Protein Kinase

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