Skip to main content

Advertisement

SpringerLink
Log in

Systemic Inflammatory Markers in Age-Associated Cognitive Impairment and Alzheimer’s Disease

  • Published:
Neuroscience and Behavioral Physiology Aims and scope Submit manuscript

Objectives. A set of immune markers reflecting different branches of multicomponent inflammatory reactions were assessed in mild cognitive impairment syndrome of the amnestic type (aMCI) in comparison with patients with Alzheimer’s disease (AD). A total of 67 patients aged 72 [63; 77] years with aMCI and 91 patients aged 74 [68; 79] years with AD were investigated. aMCI was diagnosed in accordance with the Petersen et al. (1999) criteria and the Dubois et al. (2014) criteria. Diagnoses of AD were made on the basis of ICD-10 and NINCDS-ADRDA criteria. The severity of dementia was determined on the basis of clinical signs using the CDR (Clinical Dementia Rating) scales and total Mini Mental State Examination (MMSE) scores. The control group consisted of 38 subjects with age and gender comparable to those of the study groups. Immunobiochemical investigations were performed using plasma. Leukocyte elastase (LE) and α1-proteinase inhibitor (α1-PI) activities were estimated spectrophotometrically and interleukin-6 (IL-6) and C-reactive protein (CRP) levels were measured using an immunoenzyme method. Results. A significant decrease in LE activity was seen in the AD group (p < 0.0001), along with increases in the activity/ levels of acute-phase proteins (α1-PI and CRP) and IL-6 (p < 0.0001, p < 0.05, and p < 0.01, respectively). Clinical-biochemical correlations were found between CDR, MMSE, and LE activity (r = –0.38, r = 0.31, p < 0.05), i.e., the more severe the cognitive decline in the state of dementia, as reflected in the MMSE and clinical symptoms, the lower the level of LE activity. Among patients with aMCI, there were significant increases in the activity/levels of α1-PI and IL-6 (p < 0.0001, p < 0.01), while only 30% of patients showed the spectrum of inflammatory markers typical of patients with AD. Conclusions. The results of this comparative analysis of the spectrum of inflammatory markers in patients with aMCI and AD suggest that about a third of aMCI patients constitute a group at extremely high risk of developing AD and require follow-up with regular assessment of the state of cognitive functions and, perhaps, of preventive therapy.

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. Y. J. Lee, S. B. Han, S. Y. Nam, et al., “Inflammation and Alzheimer’s disease,” Arch. Pharm. Res., 33, No. 10, 1539–1556 (2010), https://doi.org/10.1007/s12272-010-1006-7.

    Article  CAS  PubMed  Google Scholar 

  2. L. Tay, W. S. Lim, M. Chan, et al., “The independent role of inflammation in physical frailty among older adults with mild cognitive impairment and mild-to-moderate Alzheimer’s disease,” J. Nutr. Health Aging, 20, No. 3, 288–299 (2016), https://doi.org/10.1007/s12603-015-0617-6.

    Article  CAS  PubMed  Google Scholar 

  3. E. Dursun, D. Gezen-Ak, H. Hanağası, et al., “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 (2015), https://doi.org/10.1016/j.jneuroim.2015.04.014.

    Article  CAS  PubMed  Google Scholar 

  4. K. Yaffe, A. Kanaya, K. Lindquist, et al., “The metabolic syndrome, inflammation, and risk of cognitive decline,” JAMA, 292, No. 18, 2237–2242 (2004).

    Article  CAS  PubMed  Google Scholar 

  5. D. Kempuraj, R. Thangavel, P. A. Natteru, et al., “Neuroinflammation Induces Neurodegeneration,” J. Neurol. Neurosurg. Spine, 1, No. 1, 1003 (2016).

    PubMed  PubMed Central  Google Scholar 

  6. S. I. Gavrilova, “Approaches to the preventive therapy of Alzheimer’s disease: challenges and possibilities,” Psikhiatriya, 61, No. 01, 5–12 (2014).

    Google Scholar 

  7. A. Gabelle, I. Jaussent, C. Hirtz, et al., “Cerebrospinal fluid levels of orexin-A and histamine, and sleep profile within the Alzheimer process,” Neurobiol. Aging, 53, 59–66 (2017), https://doi.org/10.1016/j.neurobiolaging.2017.01.011.

    Article  CAS  PubMed  Google Scholar 

  8. O. H. Al-Jiffri, F. M. Al-Sharif, E. H. Al-Jiffri, and V. N. Uversky, “Intrinsic disorder in biomarkers of insulin resistance, hypoadiponectinemia, and endothelial dysfunction among the type 2 diabetic patients,” Intrinsically Disord. Proteins, 4, No. 1, e1171278 (2016), https://doi.org/10.1080/21690707.2016.1171278.

    Article  PubMed  PubMed Central  Google Scholar 

  9. S. Piirainen, A. Youssef, C. Song, et al., “Psychosocial stress on neuroinflammation and cognitive dysfunctions in Alzheimer’s disease: the emerging role for microglia?” Neurosci. Biobehav. Rev., 77, 148–164 (2017), https://doi.org/10.1016/j.neubiorev.2017.01.046.

    Article  CAS  PubMed  Google Scholar 

  10. B. S. Ashok, T. A. Ajith, and S. Sivanesan, “Hypoxia-inducible factors as neuroprotective agent in Alzheimer’s disease,” Clin. Exp. Pharmacol. Physiol., 44, No. 3, 327–334 (2017), https://doi.org/10.1111/1440-1681.12717.

    Article  CAS  PubMed  Google Scholar 

  11. E. M. Ribe and S. Lovestone, “Insulin signalling in Alzheimer’s disease and diabetes: from epidemiology to molecular links,” J. Intern. Med., 280, No. 5, 430–442 (2016), https://doi.org/10.1111/joim.12534.

    Article  CAS  PubMed  Google Scholar 

  12. M. Bozluolcay, G. Andican, S. Fırtına, et al., “Inflammatory hypothesis as a link between Alzheimer’s disease and diabetes mellitus,” Geriatr. Gerontol. Int., 16, No. 10, 1161–1166 (2016), https://doi.org/10.1111/ggi.12602.

    Article  PubMed  Google Scholar 

  13. M. A. Pal’tsev (ed.), Lectures in General Pathological Anatomy: Textbook, Russkii Vrach, Moscow (2003).

    Google Scholar 

  14. V. R. Varma, S. Varma, Y. An, et al., “Alpha-2 macroglobulin in Alzheimer’s disease: a marker of neuronal injury through the RCAN1 pathway,” Mol. Psychiatry, 22, No. 1, 13–23 (2017), https://doi.org/10.1038/mp.2016.206.

    Article  CAS  PubMed  Google Scholar 

  15. M. T. Schram, S. M. Euser, A. J. de Craen, et al., “Systemic markers of inflammation and cognitive decline in old age,” J. Am. Geriatr. Soc., 55, No. 5, 708–716 (2007), https://doi.org/10.1111/j.1532-5415.2007.01159.x.

    Article  PubMed  Google Scholar 

  16. P. Komulainen, T. A. Lakka, M. Kivipelto, et al., “Serum high sensitivity C-reactive protein and cognitive function in elderly women,” Age Ageing, 36, No. 4, 443–448 (2007).

    Article  PubMed  Google Scholar 

  17. L. V. Androsova, N. M. Mikhaylova, S. A. Zozulya, et al., “Inflammatory makers in Alzheimer’s disease and vascular dementia,” Zh. Nevrol. Psikhiat., 113, No. 2, 49–53 (2013).

    CAS  Google Scholar 

  18. T. P. Kliushnik, L. V. Androsova, N. M. Mikhaylova, et al., “Potential markers for Alzheimer’s disease associated with inflammation,” Psikhiatriya, 61, No. 1, 26–32 (2014).

    Google Scholar 

  19. L. Androsova, N. Mikhaylova, S. Zozulya, et al., “A comparative study of innate immunity markers in Alzheimer’s disease, Mixed dementia and Vascular dementia,” Int. J. Clin. Neurosci. Ment. Health, 3, Suppl. 1, 03 (2016), https://doi.org/10.21035/ijcnmh.2016.3 (Suppl.1).S03.

  20. R. C. Petersen, G. E. Smith, S. C. Waring, et al., “Mild cognitive impairment: clinical characterization and outcome,” Arch. Neurol., 56, No. 3, 303–308 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. B. Dubois and M. L. Albert, “Amnestic MCI or prodromal Alzheimer’s disease,” Lancet Neurol., 3, 246–248 (2004).

    Article  PubMed  Google Scholar 

  22. B. Dubois, H. H. Feldman, C. Jacova, et al., “Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria,” Lancet Neurol., 13, No. 6, 614-629 (2014), https://doi.org/10.1016/S1474-4422(14)70090-0.

    Article  PubMed  Google Scholar 

  23. G. McKhann, D. Drachman, M. Folstein, et al., “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, 34, No. 7, 939–944 (1984).

    Article  CAS  PubMed  Google Scholar 

  24. C. P. Hughes, L. Berg, W. L. Danziger, et al., “A new clinical scale for the staging of dementia,” Br. J. Psychiatr., 140, No. 3, 566–572 (1982).

    Article  CAS  Google Scholar 

  25. M. F. Folstein, S. F. Folstein, and P. R. McHugh, “Mini-Mental State. A practical method for grading the cognitive state of patients for the clinician,” J. Psychiatr. Res., 12, 189–198 (1975).

    Article  CAS  PubMed  Google Scholar 

  26. V. L. Dotsenko, E. A. Neshkova, and G. A. Yarovaya, “Detection of human leukocyte elastase from the complex with plasma α1-proteinase inhibitor on the basis of its enzyme activity with a synthetic substrate,” Vopr. Med. Khim., 40, No. 3, 20–25 (1994).

    CAS  PubMed  Google Scholar 

  27. V. F. Nartikova and T. S. Paskhina, “A unified method for assay of human serum (plasma) α1-antitrypsin and α2-macroglobulin activity,” Vopr. Med. Khimii, 25, No. 4, 494–499 (1979).

    CAS  PubMed  Google Scholar 

  28. S. I. Gavrilova, Ya. B. Fedorova, I. F. Roshchina, and G. I. Korovaitseva, “Prognosis of mild cognitive impairment syndrome on the basis of data from a two-year clinical follow-up study,” Zh. Nevrol. Psikhiat., 107, No. 1, 1–11 (2007).

    Google Scholar 

  29. A. Le Page, J. Lamoureux, K. Bourgade, et al., “Immune signatures of Alzheimer’s disease: profiles of neutrophils. (HUM 1P.301),” J. Immunol., 194, Suppl. 1, 52.26 (2015).

    Google Scholar 

  30. S. H. Baik, M. Y. Cha, Y. M. Hyun, et al., “Migration of neutrophils targeting amyloid plaques in Alzheimer’s disease mouse model,” Neurobiol. Aging, 35, No. 6, 1286–1292 (2014), https://doi.org/10.1016/j.neurobiolaging.2014.01.003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. E. Zenaro, E. Pietronigro, V. Della Bianca, et al., “Neutrophils promote Alzheimer’s disease -like pathology and cognitive decline via LFA-1 integrin,” Nat. Med., 21, No. 8, 880–886 (2015), https://doi.org/10.1038/nm.3913.

    Article  CAS  Google Scholar 

  32. T. G. Fong, D. Davis, M. E. Growdon, et al., “The interface between delirium and dementia in elderly adults,” Lancet Neurol., 14, No. 8, 823–832 (2015), https://doi.org/10.1016/S14744422(15)00101-5.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Mental Health Research Center, Moscow, Russia

    T. P. Kliushnik, L. V. Androsova, N. M. Mikhaylova, I. V. Kolykhalov, S. A. Zozulya & A. M. Dupin

Authors
  1. T. P. Kliushnik
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. V. Androsova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. N. M. Mikhaylova
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. I. V. Kolykhalov
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. S. A. Zozulya
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. M. Dupin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to T. P. Kliushnik.

Additional information

Translated from Zhurnal Nevrologii i Psikhiatrii imeni S. S. Korsakova, Vol. 117, No. 7, Iss. 1, pp. 74–79, July, 2017.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kliushnik, T.P., Androsova, L.V., Mikhaylova, N.M. et al. Systemic Inflammatory Markers in Age-Associated Cognitive Impairment and Alzheimer’s Disease. Neurosci Behav Physi 49, 352–356 (2019). https://doi.org/10.1007/s11055-019-00739-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-019-00739-7

Keywords

Search

Navigation