Immunophenotypic characteristics of peripheral blood monocytes in patients with Alzheimer's disease and mild cognitive impairment syndrome

Aim: to study the features of subpopulation composition of peripheral blood monocytes in patients with Alzheimer's disease (AD) and with amnesic mild cognitive impairment syndrome (aMCI).
Material and methods: 20 AD patients aged 73.8 ± 6.8 years, and 10 patients with aMCI aged 61.8 ± 9.6 years enrolled in the study were examined. 16 mentally and somatically healthy age- and gender-matched persons were examined as controls. The peripheral venous blood of patients and controls was the material for the study. The relative number of monocytes was determined with the help of FC-500 Flow Суtofluorometer [Beckman Coulter, USA] using the same settings for all samples.
Results: the study revealed a significant decrease of the relative number of classical subpopulations (p < 0.01) and an increase of the proinflammatory monocytes level (p < 0.01) in the group of AD patients compared with the control group. The severity of changes of the monocytes subpopulation composition depended on the dementia severity. The sharpest change of the  monocytes composition compared to controls was typical for patients with moderate dementia (p < 0.001). An increase of the subpopulation level of proinflammatory monocytes was also revealed in patients with aMCI (p < 0.05).
Conclusion: the study results have revealed the redistribution of monocyte subpopulations in AD and aMCI patients: the decrease in the classical monocytes subpopulation on the background of the increase of the monocytes subpopulation with proinflammatory activity.

1. Gu B.J., Huang X., Ou A., Rembach A., Fowler C., Avula P.K., Horton A., Doeke J.D., Villemagne V.L., Macaulay S.L., Maruff P., Fletcher E.L., Guymer R., Wiley J.S., Masters C.L. Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer,s disease. Acta Neuropathol. 2016;132:377–389. DOI: 10.1007/s00401-016-1596-3

2. Vlasenko A.G., Minton M.A. In vivo beta-amiloid imaging of the human brain. Annaly Klinicheskoy I Experimental'noy Nevrologii. 2009;3(2):37–41. (In Russ.). https://elibrary.ru/download/elibrary_12967685_16268746.pdf

3. Kolyaskina G.I., Androsova L.V., Sekirina T.P., Kushner S.G., Burbayeva O.A., Vasil'yeva Ye.F., Gavrilova S.I., Selezneva N.D. Funktsiya immunnoy sistemy pri starenii i bolezni Al'tsgeymera Materialy Vtoroy Rossiyskoy konferentsii «Bolezn' Al'tsgeymera i stareniye: ot neyrobiologii k terapii» p/r S.I. Gavrilovoy. Moskva; 1999:59–63. (In Russ.). http://old.ncpz.ru/lib/54/book/1/chapter/9

4. Kuo Y.M., Emmerling M.R., Vigo-Pelfrey C., Kasunic T.C., Kirkpatrick J.B., Murdoch G.H., Ball M.J., Roher A.El. Water-soluble Abeta (N-40, N-42) oligomers in normal and Alzheimer disease brains. Journal of Biological Chemistry.1996;271:4077–4081. DOI: 10.1074/jbc.271.8.4077

5. Androsova L.V., Mikhaylova N.M., Zozulya S.A., Dupin A.M., Rassadina G.A., Lavrent'yeva N.V., Klyushnik T.P. Inflammatory markers in schizophrenia in aged. Zhurnal neuropathology and psychiatry im. S.S. Korsakova. 2013;113(2):49–53. (In Russ.). DOI: 10.1007/s00401-016–1596–3.

6. Klyushnik T.P., Androsova L.V., Dupin A.M. Vrozhdennyy immunitet i bolezn' Al'tsgeymera. Psikhiatriya. 2011;1:52–58. (In Russ.). http://ncpz.ru/siteconst/userfiles/file/psy/Psy49.pdf

7. Fiala M., Lin J., Ringman J., Kermani-Arab V., Tsao G., Patel A., Lossinsky A.S., Graves A., Savre J., Sofroni E., Suarez T., Chiappelli F., Bernard G. Inneffective phagocytosis of amyloid-beta by macrophages of Alzheimer,s disease patients. J. Alzheimers Dis. 2005;7(3):221–232. PMID: 16006665

8. Cashman J.R., Ghirmai S., Abel K.J., Fialo M. Immue defects in Alzheimer,s disease :new medications development. BMC Neuroscience. 2008;9(2):13–20. DOI: 10.1186/1471-2202-9-s2-313.

9. Darlington D., Li S., Hou H.,Habib A., Tian J., Gao Y., Ehrhart J., Sanberg PR., Sawmiller D., Guinta B., Mori T., Tan J. Human umbical cord blood-derived monocytes improve cognitive deficits and reduce amyloid-beta pathology in PSAPP mice. Cell. Transplant. 2015;24(11):2237–2250. DOI: 10.3727/096368915X688894. Epub 2015 Jul 30.

10. Gu B.J., Huang X., Ou A., Rembach A., Fowler C., Avula P.K., Horton A., Doeke J.D., Villemagne V.L., Macaulay S.L., Maruff P., Fletcher E.L., Guymer R., Wiley J.S., Masters C.L. Innate phagocytosis by peripheral blood monocytes is altered in Alzheimer,s disease. Acta Neuropathol. 2016;132:377–389. DOI: 10.1007/s00401-016-1596-3

11. Gavrilova S.I., Fedorova I.B., Roshchina I.F., Korovaĭtseva G.I. Prognosis of the syndrome of mild cognitive impairment: the data of the biennial follow-up study. Zhurnal Nevrol Psikhiatr Im. S.S. Korsakova. 2007;107(1):1–11. (In Russ.). https://elibrary.ru/item.asp?id=9316425

12. Kolyaskina G.I., Androsova L.V., Sekirina T.P., Kushner S.G., Burbayeva O.A., Vasil'yeva Ye.F., Gavrilova S.I., Selezneva N.D. Funktsiya immunnoy sistemy pri starenii i bolezni Al'tsgeymera Materialy Vtoroy Rossiyskoy konferentsii «Bolezn' Al'tsgeymera i stareniye: ot neyrobiologii k terapii» p/r S.I. Gavrilovoy. Moskva; 1999:59–63. (In Russ.). http://old.ncpz.ru/lib/54/book/1/chapter/9

13. Matveyeva V.G., Golovin A.S., Grigor'yev Ye.V., Antonova L.V. Osobennosti dinamiki subpopulyatsionnogo sostava monotsitov pri aktivatsii. Rossiyskiy immunologicheskiy zhurnal, 2014;8(17) 4:1028–1034. (In Russ.). http://naukarus.com/osobennosti-dinamiki-subpopulyatsionnogo-sostava-monotsitov-pri-aktivatsii

14. Androsova L.V., Mikhaylova N.M., Zozulya S.A., Dupin A.M., Rassadina G.A., Lavrent'yeva N.V., Klyushnik T.P. Inflammatory markers in schizophrenia in aged. Zhurnal neuropathology and psychiatry im. S.S. Korsakova. 2013;113(2):49–53. (In Russ.). DOI: 10.1007/s00401-016–1596–3.

15. Tallone T., Turcjni G., Soldati G., Pedrozini G., Moccetti T., Vassalli G. Heterogeneity of human monocytes: an optimized four — color flow cytometry protocol for analysis of monocyte subsets. Journal of Cardiovascular Translational Research. 2011;4(2):211–219. DOI: 10.1007/s12265-011-9256–4

16. Fiala M., Lin J., Ringman J., Kermani-Arab V., Tsao G., Patel A., Lossinsky A.S., Graves A., Savre J., Sofroni E., Suarez T., Chiappelli F., Bernard G. Inneffective phagocytosis of amyloid-beta by macrophages of Alzheimer,s disease patients. J. Alzheimers Dis. 2005;7(3):221–232. PMID: 16006665

17. Ziegler-Heitbrock L. The CD14+CD16+ blood monocytes: there role in infection and inflammation. Journal of Leucocyte Biology. 2007;81(3):584–592. DOI: 10.1189/jlb.0806510

18. Darlington D., Li S., Hou H.,Habib A., Tian J., Gao Y., Ehrhart J., Sanberg PR., Sawmiller D., Guinta B., Mori T., Tan J. Human umbical cord blood-derived monocytes improve cognitive deficits and reduce amyloid-beta pathology in PSAPP mice. Cell. Transplant. 2015;24(11):2237–2250. DOI: 10.3727/096368915X688894. Epub 2015 Jul 30.

19. Wang S.Y., Mak K.L., Chen L.Y., Chou M.P., Ho C.K. Heterogeneity of human blood monocytes: two subpopulations with differents sizes, phenotypes and function. Immunology. 1992;77(2):298–303. PMID: 1427982.

20. Gavrilova S.I., Fedorova I.B., Roshchina I.F., Korovaĭtseva G.I. Prognosis of the syndrome of mild cognitive impairment: the data of the biennial follow-up study. Zhurnal Nevrol Psikhiatr Im. S.S. Korsakova. 2007;107(1):1–11. (In Russ.). https://elibrary.ru/item.asp?id=9316425

21. Ziegler-Heitbrock L., Ancuta P., Crowe S., Dalod M., Grau V., Hart D.N., Leenen P.J., Liu Y.J., MacPherson G., Randolph G.J., Scherberich J., Schmitz J., Shortman K., Sozzani S., Strobl H., Zembala M., Austyn J.M., Lutz M.B. Nomenclature of monocytes and dendritic cells in blood. Blood. 2010;116(16):74–80. DOI: https://doi.org/10.1182/blood-2010-02-258558

22. Matveyeva V.G., Golovin A.S., Grigor'yev Ye.V., Antonova L.V. Osobennosti dinamiki subpopulyatsionnogo sostava monotsitov pri aktivatsii. Rossiyskiy immunologicheskiy zhurnal, 2014;8(17) 4:1028–1034. (In Russ.). http://naukarus.com/osobennosti-dinamiki-subpopulyatsionnogo-sostava-monotsitov-pri-aktivatsii

23. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E.M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34(7):939–944. DOI:10.1212/WNL.34.7.939

24. Tallone T., Turcjni G., Soldati G., Pedrozini G., Moccetti T., Vassalli G. Heterogeneity of human monocytes: an optimized four — color flow cytometry protocol for analysis of monocyte subsets. Journal of Cardiovascular Translational Research. 2011;4(2):211–219. DOI: 10.1007/s12265-011-9256–4

25. Hughes C.P., Berg L., Danziger W.L., Coben L.A., Martin R.L. A new clinical scale for the staging of dementia. Br. J. Psychiatr. 1982;140:3:566–572. DOI:10.1212/WNL.34.7.939

26. Ziegler-Heitbrock L. The CD14+CD16+ blood monocytes: there role in infection and inflammation. Journal of Leucocyte Biology. 2007;81(3):584–592. DOI: 10.1189/jlb.0806510

27. Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolyan Areg A. Standartizirovannaya tekhnologiya «Issledovaniye subpopulyatsionnogo sostava limfotsitov perifericheskoy krovi s primeneniyem protochnykh tsitoflyuorimetrov-analizatorov» (proyekt). Meditsinskaya immunologiya. 2012;14(3):255–268. (In Russ.). https://elibrary.ru/download/elibrary_17659006_51905648.pdf

28. Wang S.Y., Mak K.L., Chen L.Y., Chou M.P., Ho C.K. Heterogeneity of human blood monocytes: two subpopulations with differents sizes, phenotypes and function. Immunology. 1992;77(2):298–303. PMID: 1427982.

29. Luider J.I., Cyfra M., Johnson P., Auer I. Impact of the new Beckman Coulter Cytomics FC-500 5-color flow cytometer on a regional flow cytometry clinical laboratory service. Lab. Hematol. 2004;10:102–108. DOI:10.1532/LH96.0421

30. Ziegler-Heitbrock L., Ancuta P., Crowe S., Dalod M., Grau V., Hart D.N., Leenen P.J., Liu Y.J., MacPherson G., Randolph G.J., Scherberich J., Schmitz J., Shortman K., Sozzani S., Strobl H., Zembala M., Austyn J.M., Lutz M.B. Nomenclature of monocytes and dendritic cells in blood. Blood. 2010;116(16):74–80. DOI: https://doi.org/10.1182/blood-2010-02-258558

31. Maecker H., McCoy P., Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat. Rev. Immunol. 2012;12:191–200. DOI:10.1038/nri3158.

32. McKhann G., Drachman D., Folstein M., Katzman R., Price D., Stadlan E.M. Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer's Disease. Neurology. 1984;34(7):939–944. DOI:10.1212/WNL.34.7.939

33. Hughes C.P., Berg L., Danziger W.L., Coben L.A., Martin R.L. A new clinical scale for the staging of dementia. Br. J. Psychiatr. 1982;140:3:566–572. DOI:10.1212/WNL.34.7.939

34. Khaydukov S.V., Baydun L.A., Zurochka A.V., Totolyan Areg A. Standartizirovannaya tekhnologiya «Issledovaniye subpopulyatsionnogo sostava limfotsitov perifericheskoy krovi s primeneniyem protochnykh tsitoflyuorimetrov-analizatorov» (proyekt). Meditsinskaya immunologiya. 2012;14(3):255–268. (In Russ.). https://elibrary.ru/download/elibrary_17659006_51905648.pdf

35. Luider J.I., Cyfra M., Johnson P., Auer I. Impact of the new Beckman Coulter Cytomics FC-500 5-color flow cytometer on a regional flow cytometry clinical laboratory service. Lab. Hematol. 2004;10:102–108. DOI:10.1532/LH96.0421

36. Maecker H., McCoy P., Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat. Rev. Immunol. 2012;12:191–200. DOI:10.1038/nri3158.