Immune blood biomarkers of Alzheimer disease patients

Avagyan, Hripsime; Goldenson, Benjamin; Tse, Eric; Masoumi, Ava; Porter, Verna; Wiedau‐Pazos, Martina; Sayre, James W.; Ong, Reno; Mahanian, Michelle; Koo, Patrick; Bae, Sangmee; Mićić, Miodrag; Liu, Philip T.; Rosenthal, Mark J.; Fiala, Milan

doi:10.1016/j.jneuroim.2009.02.015

Cited by 54 publications

(66 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Aβ uptake and degradation depend upon microglia/macrophages, but macrophages of AD patients are defective in Aβ binding and uptake [11] and Aβ degradation [12]. Peripheral macrophages have also been shown to infiltrate the AD brain [13].…”

Section: Introductionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients

Mizwicki

Liu

Fiala

et al. 2013

JAD

Self Cite

129

100

View full text Add to dashboard Cite

As immune defects in amyloid-β (Aβ) phagocytosis and degradation underlie Aβ deposition and inflammation in Alzheimer’s disease (AD) brain, better understanding of the relation between Aβ phagocytosis and inflammation could lead to promising preventive strategies. We tested two immune modulators in peripheral blood mononuclear cells (PBMCs) of AD patients and controls: 1α,25(OH)2-vitamin D3 (1,25D3) and resolvin D1 (RvD1). Both 1,25D3 and RvD1 improved phagocytosis of FAM-Aβ by AD macrophages and inhibited fibrillar Aβ-induced apoptosis. The action of 1,25D3 depended on the nuclear vitamin D and the protein disulfide isomerase A3 receptors, whereas RvD1 required the chemokine receptor, GPR32. The activities of 1,25D3 and RvD1 commonly required intracellular calcium, MEK1/2, PKA, and PI3K signaling; however, the effect of RvD1 was more sensitive to pertussis toxin. In this case study, the AD patients: a) showed significant transcriptional up regulation of IL1RN, ITGB2, and NFκB; and b) revealed two distinct groups when compared to controls: group 1 decreased and group 2 increased transcription of TLRs, IL-1, IL1R1 and chemokines. In the PBMCs/macrophages of both groups, soluble Aβ (sAβ) increased the transcription/secretion of cytokines (e.g., IL1 and IL6) and chemokines (e.g., CCLs and CXCLs) and 1,25D3/RvD1 reversed most of the sAβ effects. However, they both further increased the expression of IL1 in the group 1, sβ-treated cells. We conclude that in vitro, 1,25D3 and RvD1 rebalance inflammation to promote Aβ phagocytosis, and suggest that low vitamin D3 and docosahexaenoic acid intake and/or poor anabolic production of 1,25D3/RvD1 in PBMCs could contribute to AD onset/pathology.

show abstract

Section: Introductionmentioning

confidence: 99%

1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients

Mizwicki

Liu

Fiala

et al. 2013

JAD

Self Cite

129

100

View full text Add to dashboard Cite

show abstract

“…[56][57][58][59] Studies using in vitro cell culture models have shown enhanced phagocytic activity following treatment with Zingiberaceae spices associated with increased expression of genes involved in pathogen recognition and uptake. [20,21,25] Similar studies with ginger (Zingiber officinale) have also shown to significantly increase in pathogen uptake and [22,60] observed significant increases in phagocytosis and extracellular respiratory burst in leukocytes isolated from rainbow trout treated with 1.0% aqueous ginger extract for three weeks. In another study, Figure 6: Fold change in total nitrates (NOx) in coelomic fluid of L. terrestris in response to ginger (G), turmeric (T), cyclophosphamide (CP) and cyclophosphamide-spice (CP-G and CP-T) cotreatment.…”

Section: Discussionmentioning

confidence: 80%

Dietary supplementation with two Zingiberaceae spices ginger and turmeric modulates innate immunity parameters in Lumbricus terrestris

Vattem¹,

Lester²,

DeLeon³

et al. 2012

J Nat Pharm

View full text Add to dashboard Cite

Introduction: Zingiberaceae spices are important in diet and are well known for their health promoting effects. However, their effect on modulation of innate immunity is not very well understood. Objective: The effect of two dietary Zingiberaceae spices (ginger and turmeric) on innate immunological parameters was investigated in Lumbricus terrestris. Materials and Methods: Animals fed ad libitum on Lumbricus growth medium supplemented with 0.1% (w/v) and 0.5% (w/v) of spices for 6 days. Relative fold changes in total coelomic cell counts, coelomic cell viability and relative neutrophil-like cell counts were determined in response to spice treatment. Fold changes in nitric oxide, phagocytic activity (PA) and respiratory burst index (RBI) were determined in response to spice treatment relative to control. Effect of spices on suppression of immunological functions in response to treatment with cyclophosphamide (50 mg/ kg-BW) was also evaluated. Results: Our results indicate that dietary supplementation of Zingiberaceae spices significantly increased the coelomcyte number, viability and their differentiation into neutrophil-like cells. An increase in coelomic fluid nitric oxide level in response to dietary supplementation with ginger and turmeric, may explain these effects. Spice treatments also resulted in coelomcytes that had significantly higher PA relative to control. Surprisingly, the RBI increased nonexponentially in response to spice treatments suggesting a potential enhancement in pathogen recognition and antioxidant defenses. Moreover, cotreatment with spices abrogated immunosuppressive effects of CP in L. terrestris and improved immunological functions. Conclusion: Zingiberaceae spices may have beneficial immunomodulatory properties with potential applications in wound healing, antibiotic and cancer chemotherapy.

show abstract

“…42,43 Patients with Alzheimer's disease and a mouse model of Alzheimer's have been shown to have increased BBB permeability. 44,45 Patients have also been shown to have TLR induction, 46,47 activated microglia 48 and upregulated expression of cytokines, chemokines and chemokine receptors. 49 In diseased individuals with neuroinfections, such has HIV, the BBB has been shown to be more permeable.…”

Section: Current Understanding Of the Immune Responses In The Cnsmentioning

confidence: 99%

“…Although there is no evidence to support a function for any particular cytokine in the direct triggering of any of these neurodegenerative conditions, cytokine-driven neuroinflammation and neurotoxicity has been shown to modify disease progression in a number of these disorders. [42][43][44][46][47][48][49][50][51][52] Regardless of the initiating factor once an inflammatory response is initiated if left unresolved, it may contribute to death of vulnerable neuronal populations.…”

Section: Current Understanding Of the Immune Responses In The Cnsmentioning

confidence: 99%

Progress and prospects: Immunobiology of gene therapy for neurodegenerative disease: prospects and risks

McMenamin

Wood

2010

Gene Ther

View full text Add to dashboard Cite

Gene therapy for neurological, and in particular neurodegenerative, disease is now a reality. A number of early phase clinical trials have been completed and several are currently in progress. In view of this, it is critically important to evaluate the immunological risk associated with neurological gene therapy, which has clear implications for trial safety and efficacy. Moreover, it is imperative in particular to identify factors indicating potential high risk. In the light of recent advances in understanding immune regulation in the central nervous system (CNS) and with the continued development of new gene delivery vectors, this review critically assesses the current knowledge of immunobiology within the CNS in terms of likely immunological risk pertaining to viral vectors and gene therapy applications for neurodegenerative disease.

show abstract

Immune blood biomarkers of Alzheimer disease patients

Cited by 54 publications

References 30 publications

1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients

1α,25-Dihydroxyvitamin D3 and Resolvin D1 Retune the Balance between Amyloid-β Phagocytosis and Inflammation in Alzheimer's Disease Patients

Dietary supplementation with two Zingiberaceae spices ginger and turmeric modulates innate immunity parameters in Lumbricus terrestris

Progress and prospects: Immunobiology of gene therapy for neurodegenerative disease: prospects and risks

Contact Info

Product

Resources

About