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Plasma Amyloid-Beta Levels in Patients with Different Types of Cancer

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Abstract

Several epidemiological investigations indicate that cancer survivors have a lower risk for Alzheimer’s disease (AD) and vice versa. However, the associations between plasma amyloid-beta (Aβ) levels with cancer remain largely unknown. In this case–control study, 110 cancer patients, 70 AD patients, and 70 age- and gender-matched normal controls were recruited. The cancer types include esophagus cancer, colorectal cancer, hepatic cancer, and lung cancer, all of which were reported to be associated with a lower risk for AD. Plasma levels of Aβ40, Aβ42, common pro-inflammatory cytokines, IL-1β, IL-6, TNF-α, IFN-γ, anti-inflammatory IL-4, chemokines, and cytokines MCP-1 were measured with enzyme-linked immunosorbent assay (ELISA) kits. Plasma levels of Aβ40 and Aβ42 in all cancer patients were higher than that in normal controls. More specifically, hepatic cancer patients exhibited significantly higher plasma Aβ levels. No significant difference in plasma Aβ levels was found between chemotherapy and no chemotherapy subgroups. Plasma Aβ levels were not significantly correlated with pro-inflammatory cytokines, anti-inflammatory, chemokines, and cytokines. Peripheral Aβ levels increased in cancer patients, especially in patients with hepatic cancer, independent of chemotherapy and inflammation. Further verification is required for the association between plasma Aβ and cancer.

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References

  • Baruch K, Deczkowska A, Rosenzweig N, Tsitsou-Kampeli A, Sharif AM, et al. 2016 PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer’s disease. Nature Medicine

  • Belkhelfa M, Rafa H, Medjeber O, Arroul-Lammali A, Behairi N et al (2014) IFN-gamma and TNF-alpha are involved during Alzheimer disease progression and correlate with nitric oxide production: a study in Algerian patients. J Interf Cytokine Res 34:839–847

    Article  CAS  Google Scholar 

  • DeMattos RB, Bales KR, Cummins DJ, Dodart JC, Paul SM et al (2001) Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer’s disease. Proc Natl Acad Sci U S A 98:8850–8855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DeMattos RB, Bales KR, Cummins DJ, Paul SM, Holtzman DM (2002) Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer’s disease. Science 295:2264–2267

    Article  CAS  PubMed  Google Scholar 

  • Driver JA, Beiser A, Au R, Kreger BE, Splansky GL et al (2012) Inverse association between cancer and Alzheimer’s disease: results from the Framingham Heart Study. BMJ 344:e1442

    Article  PubMed  PubMed Central  Google Scholar 

  • Driver JA, Zhou XZ, and Lu KP. 2015 Pin1 dysregulation helps to explain the inverse association between cancer and Alzheimer’s disease. Biochim Biophys Acta

  • Dursun E, Gezen-Ak D, Hanagasi H, Bilgic B, Lohmann E et al (2015) The interleukin 1 alpha, interleukin 1 beta, interleukin 6 and alpha-2-macroglobulin serum levels in patients with early or late onset Alzheimer’s disease, mild cognitive impairment or Parkinson’s disease. J Neuroimmunol 283:50–57

    Article  CAS  PubMed  Google Scholar 

  • Frackowiak J, Miller DL, Potempska A, Sukontasup T, Mazur-Kolecka B (2003) Secretion and accumulation of Abeta by brain vascular smooth muscle cells from AbetaPP-Swedish transgenic mice. J Neuropathol Exp Neurol 62:685–696

    Article  CAS  PubMed  Google Scholar 

  • Frain L, Swanson D, Betensky R, Cho K, Gagnon D et al (2013) A reduced risk of Alzheimer’s disease is associated with the majority of cancers in a national cohort of veterans. Alzheimers Dement 9:P617

    Article  Google Scholar 

  • Ghiso J, Shayo M, Calero M, Ng D, Tomidokoro Y et al (2004) Systemic catabolism of Alzheimer’s Abeta40 and Abeta42. J Biol Chem 279:45897–45908

    Article  CAS  PubMed  Google Scholar 

  • Haass C, Schlossmacher MG, Hung AY, Vigo-Pelfrey C, Mellon A et al (1992) Amyloid beta-peptide is produced by cultured cells during normal metabolism. Nature 359:322–325

    Article  CAS  PubMed  Google Scholar 

  • Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer’s disease: progress and problems on the road to therapeutics. Science 297:353–356

    Article  CAS  PubMed  Google Scholar 

  • Hone E, Martins IJ, Fonte J, Martins RN (2003) Apolipoprotein E influences amyloid-beta clearance from the murine periphery. J Alzheimers Dis 5:1–8

    CAS  PubMed  Google Scholar 

  • Joachim CL, Mori H, Selkoe DJ (1989) Amyloid β-protein deposition in tissues other than brain in Alzheimer’s disease. Nature 341(6239):226–230

  • Lu, Jane A. Driver* and Kun Ping. 2010. Pin1: a new genetic link between Alzheimer’s disease, cancer and aging, Curr Aging Sci, 2010, 3, 158165.

    Google Scholar 

  • Martin-Rehrmann MD, Hoe HS, Capuani EM, Rebeck GW (2005) Association of apolipoprotein J-positive beta-amyloid plaques with dystrophic neurites in Alzheimer’s disease brain. Neurotox Res 7:231–242

    Article  CAS  PubMed  Google Scholar 

  • Mohammad, R. M., I. Muqbil, L. Lowe, C. Yedjou, H. Y. Hsu, et al. 2015 Broad targeting of resistance to apoptosis in cancer. Semin Cancer Biol

  • Murgas P, Godoy B, von Bernhardi R (2012) Abeta potentiates inflammatory activation of glial cells induced by scavenger receptor ligands and inflammatory mediators in culture. Neurotox Res 22:69–78

    Article  CAS  PubMed  Google Scholar 

  • Olsson B, Lautner R, Andreasson U, Ohrfelt A, Portelius E et al (2016) CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 15:673–684

    Article  CAS  PubMed  Google Scholar 

  • Rubio-Perez JM, Morillas-Ruiz JM (2012) A review: inflammatory process in Alzheimer’s disease, role of cytokines. ScientificWorldJournal 2012:756357

    Article  PubMed  PubMed Central  Google Scholar 

  • Saito Y, Saito H (2012) MicroRNAs in cancers and neurodegenerative disorders. Front Genet 3:194

    CAS  PubMed  PubMed Central  Google Scholar 

  • Serrano J, Fernandez AP, Martinez-Murillo R, Martinez A (2010) High sensitivity to carcinogens in the brain of a mouse model of Alzheimer’s disease. Oncogene 29:2165–2171

    Article  CAS  PubMed  Google Scholar 

  • Seubert P, Vigo-Pelfrey C, Esch F, Lee M, Dovey H et al (1992) Isolation and quantification of soluble Alzheimer’s beta-peptide from biological fluids. Nature 359:325–327

    Article  CAS  PubMed  Google Scholar 

  • Shoji M, Golde TE, Ghiso J, Cheung TT, Estus S et al (1992) Production of the Alzheimer amyloid beta protein by normal proteolytic processing. Science 258:126–129

    Article  CAS  PubMed  Google Scholar 

  • Suberbielle E, Djukic B, Evans M, Kim DH, Taneja P et al (2015) DNA repair factor BRCA1 depletion occurs in Alzheimer brains and impairs cognitive function in mice. Nat Commun 6:8897

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tamaki C, Ohtsuki S, Iwatsubo T, Hashimoto T, Yamada K et al (2006) Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid beta-peptide by the liver. Pharm Res 23:1407–1416

    Article  CAS  PubMed  Google Scholar 

  • Thinnes FP (2012a) Alzheimer disease controls cancer—concerning the apoptogenic interaction of cell membrane-standing type-1 VDAC and amyloid peptides via GxxxG motifs. Mol Genet Metab 106:502–503

  • Thinnes FP (2012b) Why cancer survivors have a lower risk of Alzheimer disease. Mol Genet Metab 107(2012):630–631

  • Tirumalasetti F, Han L, Birkett DP (1991) The relationship between cancer and Alzheimer’s disease. J Am Geriatr Soc 39:840

    Article  CAS  PubMed  Google Scholar 

  • White RS, Lipton RB, Hall CB, Steinerman JR (2013) Nonmelanoma skin cancer is associated with reduced Alzheimer disease risk. Neurology 80:1966–1972

    Article  PubMed  PubMed Central  Google Scholar 

  • Xiang Y, Bu XL, Liu YH, Zhu C, Shen LL et al (2015) Physiological amyloid-beta clearance in the periphery and its therapeutic potential for Alzheimer’s disease. Acta Neuropathol 130:487–499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

This study was supported by the National Natural Science Foundation of China (grant no. 81471296).

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Correspondence to Tao Zhang or Yan-Jiang Wang.

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This study was approved by the ethics committee of the Daping Hospital (Chongqing, China).

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Jin, WS., Bu, XL., Liu, YH. et al. Plasma Amyloid-Beta Levels in Patients with Different Types of Cancer. Neurotox Res 31, 283–288 (2017). https://doi.org/10.1007/s12640-016-9682-9

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  • DOI: https://doi.org/10.1007/s12640-016-9682-9

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