Myeloid Dendritic Cells Are Decreased in Peripheral Blood of Alzheimer's Disease Patients in Association with Disease Progression and Severity of Depressive Symptoms

Overview

Journal J Neuroinflammation

Publisher Biomed Central

Date 2016 Jan 27

PMID 26811068

Citations 31

Authors

Antonio Ciaramella

Francesca Salani

Federica Bizzoni

Maria Donata Orfei

Carlo Caltagirone

Gianfranco Spalletta

Paola Bossu

Affiliations

Soon will be listed here.

Abstract

Background: Dendritic cells (DCs) are major orchestrators of immune responses and inflammation. They are migratory cells, which may play a role in Alzheimer's disease (AD), as suggested by prior in vitro studies. With the intent to investigate the clinical relevance of DC modifications in vivo, the present study was aimed to evaluate the levels of blood DCs in AD patients, in relation to the progression of the disease, the severity of its symptoms, and the treatment with acetylcholinesterase inhibitors (AChEIs), a class of drugs used to improve cognitive functioning in people with dementia.

Methods: The two main subpopulations of immature blood DCs, namely myeloid (mDCs) and plasmacytoid (pDCs) cells, were evaluated by flow cytometry analysis in 106 AD patients, in comparison with the same cells from 65 individuals with mild cognitive impairment (MCI) and 73 healthy control subjects (HC). The relationship between blood DC levels and symptom severity was also assessed in AD patients, and their blood DC frequency was considered both in the absence or presence of treatment with AChEIs.

Results: A significant depletion in blood mDCs was observed in AD patients, as compared to HC and MCI subjects. At variance, pDC levels were comparable among the three groups of subjects. The mDC decrease was evident only after the emergence of AD clinical symptoms, as confirmed by the follow-up analysis of a subgroup of MCI subjects who exhibited a significant decline in mDCs after their conversion to AD. Notably, the mDC decline was inversely correlated in AD patients with the frequency and severity of depressive symptoms. Eventually, the mDC depletion was not observable in patients treated with AChEIs.

Conclusions: Our results provide the first evidence that blood mDC levels are dysregulated in AD. This phenomenon appears mainly linked to AD progression, associated with stronger severity of AD-related symptoms, and influenced by AChEI treatment. Taken all together, these data suggest that blood mDCs may serve as a cell source to test disease-induced and treatment-related changes and support the innovative notion that DCs play a role in AD, as ultimate evidence of the immune system participation in disease progression.

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References

Ciaramella A, Salani F, Bizzoni F, Orfei M, Langella R, Angelucci F . The stimulation of dendritic cells by amyloid beta 1-42 reduces BDNF production in Alzheimer's disease patients. Brain Behav Immun. 2013; 32:29-32. DOI: 10.1016/j.bbi.2013.04.001. View

Ciaramella A, Salani F, Bizzoni F, Pontieri F, Stefani A, Pierantozzi M . Blood dendritic cell frequency declines in idiopathic Parkinson's disease and is associated with motor symptom severity. PLoS One. 2013; 8(6):e65352. PMC: 3679103. DOI: 10.1371/journal.pone.0065352. View

Galgani M, Nugnes R, Bruzzese D, Perna F, De Rosa V, Procaccini C . Meta-immunological profiling of children with type 1 diabetes identifies new biomarkers to monitor disease progression. Diabetes. 2013; 62(7):2481-91. PMC: 3712055. DOI: 10.2337/db12-1273. View

Nuyts A, Lee W, Bashir-Dar R, Berneman Z, Cools N . Dendritic cells in multiple sclerosis: key players in the immunopathogenesis, key players for new cellular immunotherapies?. Mult Scler. 2013; 19(8):995-1002. DOI: 10.1177/1352458512473189. View

Pinzon-Charry A, Woodberry T, Kienzle V, McPhun V, Minigo G, Lampah D . Apoptosis and dysfunction of blood dendritic cells in patients with falciparum and vivax malaria. J Exp Med. 2013; 210(8):1635-46. PMC: 3727318. DOI: 10.1084/jem.20121972. View

Michaud J, Bellavance M, Prefontaine P, Rivest S . Real-time in vivo imaging reveals the ability of monocytes to clear vascular amyloid beta. Cell Rep. 2013; 5(3):646-53. DOI: 10.1016/j.celrep.2013.10.010. View

Goc J, Germain C, Vo-Bourgais T, Lupo A, Klein C, Knockaert S . Dendritic cells in tumor-associated tertiary lymphoid structures signal a Th1 cytotoxic immune contexture and license the positive prognostic value of infiltrating CD8+ T cells. Cancer Res. 2013; 74(3):705-15. DOI: 10.1158/0008-5472.CAN-13-1342. View

Spalletta G, Caltagirone C, Padovani A, Sorbi S, Attar M, Colombo D . Cognitive and affective changes in mild to moderate Alzheimer's disease patients undergoing switch of cholinesterase inhibitors: a 6-month observational study. PLoS One. 2014; 9(2):e89216. PMC: 3929703. DOI: 10.1371/journal.pone.0089216. View

Hu N, Tan M, Sun L, Jiang T, Wang Y, Tan L . Decreased expression of CD33 in peripheral mononuclear cells of Alzheimer's disease patients. Neurosci Lett. 2014; 563:51-4. DOI: 10.1016/j.neulet.2014.01.004. View

10.

Thewissen K, Nuyts A, Deckx N, Van Wijmeersch B, Nagels G, Dhooghe M . Circulating dendritic cells of multiple sclerosis patients are proinflammatory and their frequency is correlated with MS-associated genetic risk factors. Mult Scler. 2013; 20(5):548-57. DOI: 10.1177/1352458513505352. View

11.

Prinz M, Priller J . Microglia and brain macrophages in the molecular age: from origin to neuropsychiatric disease. Nat Rev Neurosci. 2014; 15(5):300-12. DOI: 10.1038/nrn3722. View

12.

Raj T, Rothamel K, Mostafavi S, Ye C, Lee M, Replogle J . Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science. 2014; 344(6183):519-23. PMC: 4910825. DOI: 10.1126/science.1249547. View

13.

Xia C, Peng R, Chernatynskaya A, Yuan L, Carter C, Valentine J . Increased IFN-α-producing plasmacytoid dendritic cells (pDCs) in human Th1-mediated type 1 diabetes: pDCs augment Th1 responses through IFN-α production. J Immunol. 2014; 193(3):1024-34. PMC: 4500116. DOI: 10.4049/jimmunol.1303230. View

14.

Sisirak V, Ganguly D, Lewis K, Couillault C, Tanaka L, Bolland S . Genetic evidence for the role of plasmacytoid dendritic cells in systemic lupus erythematosus. J Exp Med. 2014; 211(10):1969-76. PMC: 4172218. DOI: 10.1084/jem.20132522. View

15.

Hohsfield L, Humpel C . Migration of blood cells to β-amyloid plaques in Alzheimer's disease. Exp Gerontol. 2015; 65:8-15. PMC: 4526125. DOI: 10.1016/j.exger.2015.03.002. View

16.

Louveau A, Smirnov I, Keyes T, Eccles J, Rouhani S, Peske J . Structural and functional features of central nervous system lymphatic vessels. Nature. 2015; 523(7560):337-41. PMC: 4506234. DOI: 10.1038/nature14432. View

17.

Borovikova L, Ivanova S, Zhang M, Yang H, Botchkina G, Watkins L . Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature. 2000; 405(6785):458-62. DOI: 10.1038/35013070. View

18.

Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu Y . Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18:767-811. DOI: 10.1146/annurev.immunol.18.1.767. View

19.

Akiyama H, Barger S, Barnum S, Bradt B, Bauer J, Cole G . Inflammation and Alzheimer's disease. Neurobiol Aging. 2000; 21(3):383-421. PMC: 3887148. DOI: 10.1016/s0197-4580(00)00124-x. View

20.

Dzionek A, Fuchs A, Schmidt P, Cremer S, Zysk M, Miltenyi S . BDCA-2, BDCA-3, and BDCA-4: three markers for distinct subsets of dendritic cells in human peripheral blood. J Immunol. 2000; 165(11):6037-46. DOI: 10.4049/jimmunol.165.11.6037. View