Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and Disease    2014, Vol. 5 Issue (3) : 170-176     DOI: 10.14336/AD.2014.0500170
Raised Serum Proinflammatory Cytokines in Alzheimer’s Disease with Depression
Vineet Kumar Khemka1, Anirban Ganguly1, Debajit Bagchi1, Arindam Ghosh1, Aritri Bir1, Atanu Biswas2, Sita Chattopadhyay3, Sasanka Chakrabarti1, *
1Department of Biochemistry, Institute of Post Graduate Medical Education and Research, Kolkata, India.
2Department of Neuromedicine, Bangur Institute of Neurosciences, Kolkata, India.
3Department of Community Medicine, Institute of Post Graduate Medical Education and Research, Kolkata, India.
Download: PDF(0 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

The purpose of the present study was to identify the changes in the levels of proinflammatory cytokines like IL-1β, IL-6 and TNF-α in peripheral circulation in Alzheimer’s disease (AD) subjects and to correlate these with associated depression and cognitive deficit. Fifty five AD subjects and thirty seven age and sex matched controls were included in the study. The AD patients were grouped as AD with depression (n= 31) and AD without depression (n= 24). The serum levels of IL-1β, IL-6 and TNF-α were determined by immunoassay by commercially available kits. The serum levels of IL-6 and TNF-α were elevated in AD patients with depression compared to control (p<0.001) or AD without depression (p<0.001). The serum level of IL-1β was higher in AD patients with or without depression as compared to controls. Furthermore, a strong inverse correlation was observed between the MMSE scores and serum levels of IL-6 or TNF-α in AD subjects with depression. The study highlights the important role of peripheral IL-6 and TNF-α in AD associated depression and cognitive deficits.

Keywords Alzheimer’s disease      IL-6      IL-1β      TNF-α      Depression      Cognitive deficit     
Corresponding Authors: Sasanka Chakrabarti   
Issue Date: 10 May 2014
E-mail this article
E-mail Alert
Articles by authors
Vineet Kumar Khemka
Anirban Ganguly
Debajit Bagchi
Arindam Ghosh
Aritri Bir
Atanu Biswas
Sita Chattopadhyay
Sasanka Chakrabarti
Cite this article:   
Vineet Kumar Khemka,Anirban Ganguly,Debajit Bagchi, et al. Raised Serum Proinflammatory Cytokines in Alzheimer’s Disease with Depression[J]. Aging and Disease, 2014, 5(3): 170-176.
URL:     OR
[1] Qiu C, Fratiglioni L(2011). Epidemiology of dementia. Mcnamara P Dementia Treatments and DevelopmentsABC-CLIO1-33
[2] McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CRJr, Kawas CH(2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement, 7:263-269
[3] Starkstein SE, Mizrahi R Depression in Alzheimer’s disease. 2006). Expert Rev Neurother, 6:887-895
[4] Alvarez XA, Franco A, Fernandez-Novoa L, Cacabelos R(1996). Blood levels of histamine, IL-1β, and TNF-α in patients with mild to moderate alzheimer disease. Mol Chem Neuropathol, 29:237-252
[5] Gezen-Ak D, Dursun E, Hanagasi H, Bilgiç B, Lohman E, Araz OS(2013). BDNF, TNFα, HSP90, CFH, and IL-10 serum levels in patients with early or late onset Alzheimer’s disease or mild cognitive impairment. J Alzheimers Dis, 37:185-195
[6] Humpel C, Hochstrasser T(2011). Cerebrospinal fluid and blood biomarkers in Alzheimer’s disease. World J Psychiatry, 1:8-18
[7] Swardfager W, Lanctot K, Rothenburg L, Wong A, Capell J, Hermann NA(2010). Meta-analysis of cytokines in Alzheimer’s disease. Biol Psychiatry, 68:930-941
[8] Leonard BE(2007). Inflammation, depression and dementia: are they connected?. Neurochem Res, 32:1749-1756
[9] Anisman H(2009). Cascading effects of stressors and inflammatory immune system activation: implications for major depressive disorder. J Psychiatry Neurosci, 34:4-20
[10] Khairova RA, Machado-Vieira R, Du J, Manji HK(2009). A potential role for pro-inflammatory cytokines in regulating synaptic plasticity in major depressive disorder. Int J Neuropsycho pharmacol, 12:561-578
[11] Kronfol Z, Remick DG(2000). Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry, 157:683-694
[12] Dantzer R, O’Connor JC, Freund GG, Johnson RW, Kelley KW(2008). From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci, 9:46-56
[13] Terrando N, Monaco C, Ma D, Foxwell BM, Feldmann M, Maze M(2010). Tumor necrosis factor-alpha triggers a cytokine cascade yielding postoperative cognitive decline. Proc Natl Acad Sci U S A, 107:20518-20522
[14] Wilson CJ, Finch CE, Cohen HJ(2002). Cytokines and cognition – The case for head–to-toe inflammatory paradigm. J Am Geriatr Soc, 50:2041-2056
[15] McAfoose J, Baune BT(2009). Evidence for a cytokine model of cognitive function. Neurosci Biobehav Rev, 33:355-366
[16] Lim A, Krajina K, Marsland AL(2013). Peripheral inflammation and cognitive aging. Mod Trends Pharmacopsychiatry, 28:175-187
[17] Cameron B, Landreth GE(2010). Inflammation, microglia, and Alzheimer’s disease. Neurobiol Dis, 37:503-509
[18] Weisman D, Hakimian E, Ho GJ(2006). Interleukins, Inflammation, and Mechanisms of Alzheimer’s Disease. Vitam Horm, 74:505-530
[19] Weitz TM, Town T(2012). Microglia in Alzheimer’s Disease: It’s All About Context. Int J Alzheimers Dis, 2012:314185
[20] Mrak RE, Griffin WS(2005). Potential inflammatory biomarkers in Alzheimer’s disease. J Alzheimer’s Dis, 8:369-375
[21] Lee KS, Chung JH, Choi TK, Suh SY, Oh BH, Hong CH(2009). Peripheral cytokines and chemokines in Alzheimer’s disease. Dement Geriatr Cogn Disord, 28:281-287
[22] Barrientos RM, Frank MG, Watkins LR, Maier SF(2010). Memory Impairments in Healthy Aging: Role of Aging-Induced Microglial Sensitization. Aging Dis, 1:212-231
[23] Maier SF(2003). Bi-directional immune-brain communication: implications for understanding stress, pain, and cognition. Brain Behav Immun, 17:69-85
[24] Makhija K, Karunakaran S(2013). The role of inflammatory cytokines on the aetiopathogenesis of depression. Aust N Z J Psychiatry, 47:828-839
[25] Cyranowski JM, Marsland AL, Bromberger JT, Whiteside TL, Chang Y, Matthews KA(2007). Depressive symptoms and production of proinflammatory cytokines by peripheral blood mononuclear cells stimulated in vitro. Brain Behav Immun, 21:229-237
[26] Green RC, Cupples LA, Kurz A, Auerbach S, Go R, Sadovnick D(2003). Depression as a risk factor for Alzheimer disease - The MIRAGE study. Arch Neurol, 60:753-759
[27] Steffens DC, Plassman BL, Helms MJ, Welsh-Bohmer KA, Saunders AM, Breitner JCS(1997). A twin study of late-onset depression and apolipoprotein E ɛ4 as risk factors for Alzheimer’s disease. Biol Psychiatry, 41:851-856
[28] Devanand DP, Sano M, Tang MX, Taylor S, Gurland BJ, Wilder D, Yakov S, Mayeux R(1996). Depressed mood and the incidence of Alzheimer’s disease in the elderly living in the community. Arch Gen Psychiatry, 53:175-182
[29] Cacquevel M, Lebeurrier N, Cheenne S, Vivien D(2004). Cytokines in neuroinflammation and Alzheimer’s disease. Curr Drug Targets, 5:529-534
[30] Blasko I, Marx F, Steiner E, Hartmann T, Grubeck-Loebenstein B(1999). TNF alpha plus IFN gamma induce the production of Alzheimer beta-amyloid peptides, and decrease the secretion of APPs. FASEB J, 13:63-68
[31] Smith JA, Das A, Ray SK, Banika NL(2010). Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Research Bulletin, 87:10-20
[1] Daichi Sone,Etsuko Imabayashi,Norihide Maikusa,Masayo Ogawa,Noriko Sato,Hiroshi Matsuda,Japanese-Alzheimer’s Disease Neuroimaging Initiative. Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on 3-tesla Normal Database: Diagnostic Accuracy in Two Independent Cohorts with Early Alzheimer’s Disease[J]. A&D, 2018, 9(4): 755-760.
[2] Fabiana Morroni,Giulia Sita,Agnese Graziosi,Eleonora Turrini,Carmela Fimognari,Andrea Tarozzi,Patrizia Hrelia. Neuroprotective Effect of Caffeic Acid Phenethyl Ester in A Mouse Model of Alzheimer’s Disease Involves Nrf2/HO-1 Pathway[J]. A&D, 2018, 9(4): 605-622.
[3] Yangqi Xu,Xiaoli Liu,Junyi Shen,Wotu Tian,Rong Fang,Binyin Li,Jianfang Ma,Li Cao,Shengdi Chen,Guanjun Li,Huidong Tang. The Whole Exome Sequencing Clarifies the Genotype- Phenotype Correlations in Patients with Early-Onset Dementia[J]. A&D, 2018, 9(4): 696-705.
[4] Qiong Ding,Kitora Tanigawa,Jun Kaneko,Mamoru Totsuka,Yoshinori Katakura,Etsuko Imabayashi,Hiroshi Matsuda,Tatsuhiro Hisatsune. Anserine/Carnosine Supplementation Preserves Blood Flow in the Prefrontal Brain of Elderly People Carrying APOE e4[J]. A&D, 2018, 9(3): 334-345.
[5] Ting Shen,Yuyi You,Chitra Joseph,Mehdi Mirzaei,Alexander Klistorner,Stuart L. Graham,Vivek Gupta. BDNF Polymorphism: A Review of Its Diagnostic and Clinical Relevance in Neurodegenerative Disorders[J]. A&D, 2018, 9(3): 523-536.
[6] Fangyu Peng,Fang Xie,Otto Muzik. Alteration of Copper Fluxes in Brain Aging: A Longitudinal Study in Rodent Using 64CuCl2-PET/CT[J]. A&D, 2018, 9(1): 109-118.
[7] Diana L Castillo-Carranza,Ashley N Nilson,Candice E Van Skike,Jordan B Jahrling,Kishan Patel,Prajesh Garach,Julia E Gerson,Urmi Sengupta,Jose Abisambra,Peter Nelson,Juan Troncoso,Zoltan Ungvari,Veronica Galvan,Rakez Kayed. Cerebral Microvascular Accumulation of Tau Oligomers in Alzheimer’s Disease and Related Tauopathies[J]. A&D, 2017, 8(3): 257-266.
[8] Zohara Sternberg,Zihua Hu,Daniel Sternberg,Shayan Waseh,Joseph F. Quinn,Katharine Wild,Kaye Jeffrey,Lin Zhao,Michael Garrick. Serum Hepcidin Levels, Iron Dyshomeostasis and Cognitive Loss in Alzheimer’s Disease[J]. A&D, 2017, 8(2): 215-227.
[9] Jianhui Wang,Xiaorui Cheng,Ju Zeng,Jiangbei Yuan,Zhongfu Wang,Wenxia Zhou,Yongxiang Zhang. LW-AFC Effects on N-glycan Profile in Senescence-Accelerated Mouse Prone 8 Strain, a Mouse Model of Alzheimer’s Disease[J]. A&D, 2017, 8(1): 101-114.
[10] Annamaria Zaia,Pierluigi Maponi,Giuseppina Di Stefano,Tiziana Casoli. Biocomplexity and Fractality in the Search of Biomarkers of Aging and Pathology: Focus on Mitochondrial DNA and Alzheimer’s Disease[J]. A&D, 2017, 8(1): 44-56.
[11] Yingying Gu,Kai Zhao,Xiaoqian Luan,Zhihua Liu,Yan Cai,Qiongzhang Wang,Beilei Zhu,Jincai He. Association between Serum Magnesium Levels and Depression in Stroke Patients[J]. A&D, 2016, 7(6): 687-690.
[12] Mei-Yan Liu,Yan-Ping Ren,Li-Jun Zhang,Jamie Y. Ding. Pretreatment with Ginseng Fruit Saponins Affects Serotonin Expression in an Experimental Comorbidity Model of Myocardial Infarction and Depression[J]. A&D, 2016, 7(6): 680-686.
[13] Murat Serdar Gurses,Mustafa Numan Ural,Mehmet Akif Gulec,Omer Akyol,Sumeyya Akyol. Pathophysiological Function of ADAMTS Enzymes on Molecular Mechanism of Alzheimer’s Disease[J]. A&D, 2016, 7(4): 479-490.
[14] Ryan J. Day,Katie L. McCarty,Kayla E. Ockerse,Elizabeth Head,Troy T. Rohn. Proteolytic Cleavage of Apolipoprotein E in the Down Syndrome Brain[J]. A&D, 2016, 7(3): 267-277.
[15] Isaac G. Onyango,Jameel Dennis,Shaharyah M. Khan. Mitochondrial Dysfunction in Alzheimer’s Disease and the Rationale for Bioenergetics Based Therapies[J]. A&D, 2016, 7(2): 201-214.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd