Skip to main content

Advertisement

SpringerLink
Log in

Monocytes and Alzheimer’s disease

单核细胞和阿尔茨海默病

  • Minireview
  • Published:
Neuroscience Bulletin Aims and scope Submit manuscript

Abstract

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by extracellular amyloid beta (Aβ) deposition and intracellular neurofibrillary tangle formation. Monocyte is part of the innate immune system and can effectively remove dead cells and debris. It has been suggested that Aβ can recruit monocytes into brain in AD mice, resulting in restriction of cerebral amyloidosis. However, monocyte may act as a double-edged sword, either beneficial (e.g., clearance of Aβ) or detrimental (e.g., secretion of neurotoxic factors). In addition, recent studies indicate that in AD patients, Aβ phagocytosis by monocytes is ineffective. The present review mainly summarized the current knowledge on monocytes and their potential roles in AD.

摘要

阿尔茨海默病(Alzheimer’s disease, AD)是神经退行性疾病中最常见的类型。 胞外β淀粉样蛋白(amyloid beta, Aβ)的沉积和胞内神经原纤维的缠结是典型的AD神经病理学特征。 单核细胞是天然免疫细胞, 可以有效清除坏死细胞及碎片。 在AD模型鼠上的许多实验研究表明, Aβ可以使单核细胞向大脑募集, 从而限制脑内的淀粉样变性。 然而, 单核细胞也是一把双刃剑: 一方面它可以清除Aβ, 另一方面它又能分泌神经毒性因子, 损伤神经细胞。 此外, 近来也有研究表明, 在AD患者脑内, 单核细胞并不能有效清除Aβ沉积。 本综述主要对单核细胞及其在AD中的潜在角色进行讨论。

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Selkoe DJ. Defining molecular targets to prevent Alzheimer disease. Arch Neurol 2005, 62(2): 192–195.

    Article  PubMed  Google Scholar 

  2. Parihar MS, Hemnani T. Alzheimer’s disease pathogenesis and therapeutic interventions. J Clin Neurosci 2004, 11(5): 456–467.

    Article  CAS  PubMed  Google Scholar 

  3. Samandouras G, Teddy PJ, Cadoux-Hudson T, Ansorge O. Amyloid in neurosurgical and neurological practice. J Clin Neurosci 2006, 13(2): 159–167.

    Article  CAS  PubMed  Google Scholar 

  4. Zlokovic BV, Yamada S, Holtzman D, Ghiso J, Frangione B. Clearance of amyloid beta-peptide from brain: transport or metabolism? Nat Med 2000, 6(7): 718–719.

    Article  CAS  Google Scholar 

  5. Seta N, Kuwana M. Human circulating monocytes as multipotential progenitors. Keio J Med 2007, 56(2): 41–47.

    Article  PubMed  Google Scholar 

  6. Fiala M, Lin J, Ringman J, Kermani-Arab V, Tsao G, Patel A, et al. Ineffective phagocytosis of amyloid-beta by macrophages of Alzheimer’s disease patients. J Alzheimers Dis 2005, 7(3): 221–232; discussion 55–62.

    CAS  PubMed  Google Scholar 

  7. Hickman SE, El Khoury J. Mechanisms of mononuclear phagocyte recruitment in Alzheimer’s disease. CNS Neurol Disord Drug Targets 2010, 9(2): 168–173.

    CAS  PubMed  Google Scholar 

  8. Whitelaw DM, Batho HF. The distribution of monocytes in the rat. Cell Tissue Kinet 1972, 5(3): 215–225.

    CAS  PubMed  Google Scholar 

  9. Fogg DK, Sibon C, Miled C, Jung S, Aucouturier P, Littman DR, et al. A clonogenic bone marrow progenitor specific for macrophages and dendritic cells. Science 2006, 311(5757): 83–87.

    Article  CAS  PubMed  Google Scholar 

  10. Whitelaw DM. Observations on human monocyte kinetics after pulse labeling. Cell Tissue Kinet 1972, 5(4): 311–317.

    CAS  PubMed  Google Scholar 

  11. Gordon S, Taylor PR. Monocyte and macrophage heterogeneity. Nat Rev Immunol 2005, 5(12): 953–964.

    Article  CAS  PubMed  Google Scholar 

  12. Stöhr J, Schindler G, Rothe G, Schmitz G. Enhanced upregulation of the Fc gamma receptor IIIa (CD16a) during in vitro differentiation of ApoE4/4 monocytes. Arterioscler Thromb Vasc Biol 1998, 18(9): 1424–1432.

    PubMed  Google Scholar 

  13. Rothe G, Herr AS, Stohr J, Abletshauser C, Weidinger G, Schmitz G. A more mature phenotype of blood mononuclear phagocytes is induced by fluvastatin treatment in hypercholesterolemic patients with coronary heart disease. Atherosclerosis 1999, 144(1): 251–261.

    Article  CAS  PubMed  Google Scholar 

  14. Schmitz G, Orso E, Rothe G, Klucken J. Scavenging, signalling and adhesion coupling in macrophages: implications for atherogenesis. Curr Opin Lipidol 1997, 8(5): 287–300.

    Article  CAS  PubMed  Google Scholar 

  15. Schmitz G, Leuthauser-Jaschinski K, Orso E. Are circulating monocytes as microglia orthologues appropriate biomarker targets for neuronal diseases? Cent Nerv Syst Agents Med Chem 2009, 9(4): 307–330.

    CAS  PubMed  Google Scholar 

  16. Lutter D, Ugocsai P, Grandl M, Orso E, Theis F, Lang EW, et al. Analyzing M-CSF dependent monocyte/macrophage differentiation: expression modes and meta-modes derived from an independent component analysis. BMC Bioinformatics 2008, 9: 100.

    Article  PubMed  Google Scholar 

  17. Delamarre L, Pack M, Chang H, Mellman I, Trombetta ES. Differential lysosomal proteolysis in antigen-presenting cells determines antigen fate. Science 2005, 307(5715): 1630–1634.

    Article  CAS  PubMed  Google Scholar 

  18. Colton CA, Wilcock DM. Assessing activation states in microglia. CNS Neurol Disord Drug Targets 2010, 9(2): 174–191.

    CAS  PubMed  Google Scholar 

  19. Woollard KJ, Geissmann F. Monocytes in atherosclerosis: subsets and functions. Nat Rev Cardiol 2010, 7(2): 77–86.

    Article  PubMed  Google Scholar 

  20. Kimura S, Sawada T. Understanding the essential role of monocytes in atherosclerosis. Circ J 2010, 74(7): 1292–1293.

    Article  PubMed  Google Scholar 

  21. Nilsson J, Nordin Fredrikson G, Schiopu A, Shah PK, Jansson B, Carlsson R. Oxidized LDL antibodies in treatment and risk assessment of atherosclerosis and associated cardiovascular disease. Curr Pharm Des 2007, 13(10): 1021–1030.

    Article  CAS  PubMed  Google Scholar 

  22. Randolph GJ. The fate of monocytes in atherosclerosis. J Thromb Haemost 2009, 7Suppl 1: 28–30.

    Article  CAS  PubMed  Google Scholar 

  23. Chang CC, Wright A, Punnonen J. Monocyte-derived CD1a+ and CD1a− dendritic cell subsets differ in their cytokine production profiles, susceptibilities to transfection, and capacities to direct Th cell differentiation. J Immunol 2000, 165(7): 3584–3591.

    CAS  PubMed  Google Scholar 

  24. Lawson LJ, Perry VH, Dri P, Gordon S. Heterogeneity in the distribution and morphology of microglia in the normal adult mouse brain. Neuroscience 1990, 39(1): 151–170.

    Article  CAS  PubMed  Google Scholar 

  25. Graeber MB, Streit WJ. Perivascular microglia defined. Trends Neurosci 1990, 13(9): 366.

    Article  CAS  PubMed  Google Scholar 

  26. Soulet D, Rivest S. Microglia. Curr Biol 2008, 18(12): R506–508.

    Article  CAS  PubMed  Google Scholar 

  27. Schlachetzki JC, Hull M. Microglial activation in Alzheimer’s disease. Curr Alzheimer Res 2009, 6(6): 554–563.

    Article  CAS  PubMed  Google Scholar 

  28. Aarum J, Sandberg K, Haeberlein SL, Persson MA. Migration and differentiation of neural precursor cells can be directed by microglia. Proc Natl Acad Sci U S A 2003, 100(26): 15983–15988.

    Article  CAS  PubMed  Google Scholar 

  29. Walton MR, Gibbons H, MacGibbon GA, Sirimanne E, Saura J, Gluckman PD, et al. PU.1 expression in microglia. J Neuroimmunol 2000, 104(2): 109–115.

    Article  CAS  PubMed  Google Scholar 

  30. Ladeby R, Wirenfeldt M, Dalmau I, Gregersen R, Garcia-Ovejero D, Babcock A, et al. Proliferating resident microglia express the stem cell antigen CD34 in response to acute neural injury. Glia 2005, 50(2): 121–131.

    Article  PubMed  Google Scholar 

  31. Chan WY, Kohsaka S, Rezaie P. The origin and cell lineage of microglia: new concepts. Brain Res Rev 2007, 53(2): 344–354.

    Article  CAS  PubMed  Google Scholar 

  32. Streit WJ. Microglial activation and neuroinflammation in Alzheimer’s disease: a critical examination of recent history. Front Aging Neurosci 2010, 2: 22.

    PubMed  Google Scholar 

  33. Ajami B, Bennett JL, Krieger C, Tetzlaff W, Rossi FM. Local selfrenewal can sustain CNS microglia maintenance and function throughout adult life. Nat Neurosci 2007 10(12): 1538–1543.

    Article  CAS  PubMed  Google Scholar 

  34. D’Mello C, Le T, Swain MG. Cerebral microglia recruit monocytes into the brain in response to tumor necrosis factoralpha signaling during peripheral organ inflammation. J Neurosci 2009, 29(7): 2089–2102.

    Article  PubMed  Google Scholar 

  35. Soulet D, Rivest S. Bone-marrow-derived microglia: myth or reality? Curr Opin Pharmacol 2008, 8(4): 508–518.

    Article  CAS  PubMed  Google Scholar 

  36. Shechter R, London A, Varol C, Raposo C, Cusimano M, Yovel G, et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med 2009, 6(7): e1000113.

    Article  PubMed  Google Scholar 

  37. Hickey WF, Kimura H. Perivascular microglial cells of the CNS are bone marrow-derived and present antigen in vivo. Science 1988, 239(4837): 290–292.

    Article  CAS  PubMed  Google Scholar 

  38. Stoll G, Jander S. The role of microglia and macrophages in the pathophysiology of the CNS. Prog Neurobiol 1999, 58(3): 233–247.

    Article  CAS  PubMed  Google Scholar 

  39. Pilling D, Fan T, Huang D, Kaul B, Gomer RH. Identification of markers that distinguish monocyte-derived fibrocytes from monocytes, macrophages, and fibroblasts. PLoS One 2009, 4(10): e7475.

    Article  PubMed  Google Scholar 

  40. El Khoury J, Toft M, Hickman SE, Means TK, Terada K, Geula C, et al. Ccr2 deficiency impairs microglial accumulation and accelerates progression of Alzheimer-like disease. Nat Med 2007, 13(4): 432–438.

    Article  PubMed  Google Scholar 

  41. Frei K, Siepl C, Groscurth P, Bodmer S, Schwerdel C, Fontana A. Antigen presentation and tumor cytotoxicity by interferon-gammatreated microglial cells. Eur J Immunol 1987, 17(9): 1271–1278.

    Article  CAS  PubMed  Google Scholar 

  42. Panek RB, Benveniste EN. Class II MHC gene expression in microglia. Regulation by the cytokines IFN-gamma, TNF-alpha, and TGF-beta. J Immunol 1995, 154(6): 2846–2854.

    CAS  PubMed  Google Scholar 

  43. Shrikant P, Weber E, Jilling T, Benveniste EN. Intercellular adhesion molecule-1 gene expression by glial cells. Differential mechanisms of inhibition by IL-10 and IL-6. J Immunol 1995, 155(3): 1489–1501.

    CAS  PubMed  Google Scholar 

  44. Banati RB, Gehrmann J, Czech C, Monning U, Jones LL, Konig G, et al. Early and rapid de novo synthesis of Alzheimer beta A4-amyloid precursor protein (APP) in activated microglia. Glia 1993, 9(3): 199–210.

    Article  CAS  PubMed  Google Scholar 

  45. Simard AR, Soulet D, Gowing G, Julien JP, Rivest S. Bone marrowderived microglia play a critical role in restricting senile plaque formation in Alzheimer’s disease. Neuron 2006, 49(4): 489–502.

    Article  CAS  PubMed  Google Scholar 

  46. Town T, Laouar Y, Pittenger C, Mori T, Szekely CA, Tan J, et al. Blocking TGF-beta-Smad2/3 innate immune signaling mitigates Alzheimer-like pathology. Nat Med 2008, 14(6): 681–687.

    CAS  PubMed  Google Scholar 

  47. Guerreiro RJ, Santana I, Bras JM, Santiago B, Paiva A, Oliveira C. Peripheral inflammatory cytokines as biomarkers in Alzheimer’s disease and mild cognitive impairment. Neurodegener Dis 2007, 4(6): 406–412.

    Article  CAS  PubMed  Google Scholar 

  48. Heneka MT, Sastre M, Dumitrescu-Ozimek L, Dewachter I, Walter J, Klockgether T, et al. Focal glial activation coincides with increased BACE1 activation and precedes amyloid plaque deposition in APP[V717I] transgenic mice. J Neuroinflammation 2005, 2: 22.

    Article  PubMed  Google Scholar 

  49. Meyer-Luehmann M, Spires-Jones TL, Prada C, Garcia-Alloza M, de Calignon A, Rozkalne A, et al. Rapid appearance and local toxicity of amyloid-beta plaques in a mouse model of Alzheimer’s disease. Nature 2008, 451(7179): 720–724.

    Article  CAS  PubMed  Google Scholar 

  50. McGeer PL, McGeer EG. The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases. Brain Res Brain Res Rev 1995, 21(2): 195–218.

    Article  CAS  PubMed  Google Scholar 

  51. Grathwohl SA, Kalin RE, Bolmont T, Prokop S, Winkelmann G, Kaeser SA, et al. Formation and maintenance of Alzheimer’s disease beta-amyloid plaques in the absence of microglia. Nat Neurosci 2009, 12(11): 1361–1363.

    Article  CAS  PubMed  Google Scholar 

  52. Sanchez-Ramos J, Song S, Sava V, Catlow B, Lin X, Mori T, et al. Granulocyte colony stimulating factor decreases brain amyloid burden and reverses cognitive impairment in Alzheimer’s mice. Neuroscience 2009, 163(1): 55–72.

    Article  CAS  PubMed  Google Scholar 

  53. Conductier G, Blondeau N, Guyon A, Nahon JL, Rovère C. The role of monocyte chemoattractant protein MCP1/CCL2 in neuroinflammatory diseases. J Neuroimmunol 2010, 244(1): 93–100.

    Article  Google Scholar 

  54. Breitner JC, Welsh KA, Helms MJ, Gaskell PC, Gau BA, Roses AD, et al. Delayed onset of Alzheimer’s disease with nonsteroidal anti-inflammatory and histamine H2 blocking drugs. Neurobiol Aging 1995, 16(4): 523–530.

    Article  CAS  PubMed  Google Scholar 

  55. Mackenzie IR, Hao C, Munoz DG. Role of microglia in senile plaque formation. Neurobiol Aging 1995, 16(5): 797–804.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital, China Medical University, Shenyang, 110001, China

    Yu Feng  (冯昱) & Lei Li  (李蕾)

  2. Department of Neurology, The Fourth Affiliated Hospital, China Medical University, Shenyang, 110000, China

    Xiao-Hong Sun  (孙晓红)

Authors
  1. Yu Feng  (冯昱)
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lei Li  (李蕾)
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiao-Hong Sun  (孙晓红)
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yu Feng  (冯昱).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feng, Y., Li, L. & Sun, XH. Monocytes and Alzheimer’s disease. Neurosci. Bull. 27, 115–122 (2011). https://doi.org/10.1007/s12264-011-1205-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12264-011-1205-3

Keywords

关键词

Search

Navigation