Abstract
The expression levels of pro-inflammatory and anti-inflammatory cytokines and chemokines in blood serum of Alzheimer’s dementia patients: report from a pilot study in Kazakhstan
Aiym Kaiyrlykyzy1,2,, Gulnaz Zholdasbekova3, Dinara Alzhanova4, Farkhad Olzhayev1, Aida Baibulatova1, Andrey Tsoy1 and Sholpan Askarova1,*
1 Laboratory of Bioengineering and Regenerative Medicine, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan.
2 Faculty of Medicine and Healthcare, Al-Farabi Kazakh National University, Almaty, Kazakhstan
3 Medical University Karaganda, Karagandy, Republic of Kazakhstan
4 Department of Neurology, Medical University Astana, Nur-Sultan, Kazakhstan
* Correspondence: [email protected] (SA); [email protected] (AK).
Background
Chronic peripheral inflammation is one of the critical factors contributing significantly to the development and progression of Alzheimer’s disease (AD). Human and animal studies strongly suggest that systemic inflammation, marked by changes in the peripheral profile of blood immune cells and blood levels of circulating pro-inflammatory and anti-inflammatory cytokines, can promote or even precede pro-inflammatory conditions in the CNS. It has been reported that the levels of circulating pro-inflammatory cytokines are increased while the levels of anti-inflammatory cytokines are decreased in AD patients. However, despite increasing data supporting the association between abnormal peripheral inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. In this regards, we have studied an expanded spectrum of pro-inflammatory and anti-inflammatory cytokines and chemokines in the serum samples of the patients diagnosed with AD and compared them to those without cognitive impairment matched on age and gender.
Methods
We have simultaneously assayed cytokines and chemokines in the serum of AD patients (n=40) and normal controls (n=46) using MILLIPLEX Map Human Cytokine/Chemokine Magnetic Beas Panel on the Luminex xMAP technology according to the manufacturer’s protocol. The kit included the following 41 human cytokines and chemokines: EGF, IL-12P70, IL-13, IL-15, IL-17A, IL1RA, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, VEGF, FGF-2, TGF-α, FIT-3L, Fractalkine, GRO, MCP-3, MDC, PDGF-AA, PDGF-AB/BB, sCD40L, IL-1α, IL-1β, TNFα, G-CSF, IFNγ, TNFβ, IL-10, IL-2, GM-CSF, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, Eotaxin, IFNα2, and IL-12P40.
Results
We have found IL-12P40, IL-9, IL-7, GM-CSF, IL-10, IFNγ, IL-1α, MCP-3, FIT-3L, IL-17A, IL-13, IL-15, and IL-12P70 were significantly higher in Alzheimer’s patients compared to controls. At the same time, cognitively healthy controls had higher concentrations of PDGF-AB/BB, PDGF-AA, RANTES, and FGF-2 in the peripheral blood. We observed significant positive correlation between C-reactive protein and IP-10 (r=0.5), IL1RA (r=0.3), PDGF-AA (r=0.3), IL-10 (r=0.3), GRO (r=0.4), GCSF (r=0.3), PDGF-AB/BB (r=0.3).
Conclusion
Studying the expression levels of pro-inflammatory and anti-inflammatory cytokines and chemokines in the blood serum of Alzheimer’s dementia patients is of considerable interest since it can potentially contribute to the discovery of new blood-based biomarkers for earlier diagnosis of AD and development of the personalized treatment strategies.
1. Heneka M.T., Carson M.J., El Khoury J., Landreth G.E., Brosseron F., Feinstein D.L., Jacobs A.H., Wyss-Coray T., Vitorica J., Ransohoff R.M., Herrup K., Frautschy S.A., Finsen B., Brown G.C., Verkhratsky A., Yamanaka K., Koistinaho J., Latz E., Halle A., Petzold G.C., Town T., Morgan D., Shinohara M.L., Perry V.H., Holmes C., Bazan N.G., Brooks D.J., Hunot S., Joseph B., Deigendesch N., Garaschuk O., Boddeke E., Dinarello C.A., Breitner J.C., Cole G.M., Golenbock D.T., Kummer M.P. Neuroinflammation in Alzheimer's disease // The Lancet. Neurology. -2015. -Vol. 14. - 4. - P. 388-405.
2. Walker K.A., Ficek B.N., Westbrook R. Understanding the Role of Systemic Inflammation in Alzheimer’s Disease // ACS Chemical Neuroscience. -2019. -Vol. 10. - 8. - P. 3340-3342.
3. Xie J., Van Hoecke L., Vandenbroucke R.E. The Impact of Systemic Inflammation on Alzheimer’s Disease Pathology // Frontiers in Immunology. -2022. -Vol. 12.
4. Park J.C., Han S.H., Mook-Jung I. Peripheral inflammatory biomarkers in Alzheimer's disease: a brief review // BMB Rep. -2020. -Vol. 53. - 1. - P. 10-19.
Aiym Kaiyrlykyzy1,2,, Gulnaz Zholdasbekova3, Dinara Alzhanova4, Farkhad Olzhayev1, Aida Baibulatova1, Andrey Tsoy1 and Sholpan Askarova1,*
1 Laboratory of Bioengineering and Regenerative Medicine, Center for Life Sciences, National Laboratory Astana, Nazarbayev University, Nur-Sultan, Kazakhstan.
2 Faculty of Medicine and Healthcare, Al-Farabi Kazakh National University, Almaty, Kazakhstan
3 Medical University Karaganda, Karagandy, Republic of Kazakhstan
4 Department of Neurology, Medical University Astana, Nur-Sultan, Kazakhstan
* Correspondence: [email protected] (SA); [email protected] (AK).
Background
Chronic peripheral inflammation is one of the critical factors contributing significantly to the development and progression of Alzheimer’s disease (AD). Human and animal studies strongly suggest that systemic inflammation, marked by changes in the peripheral profile of blood immune cells and blood levels of circulating pro-inflammatory and anti-inflammatory cytokines, can promote or even precede pro-inflammatory conditions in the CNS. It has been reported that the levels of circulating pro-inflammatory cytokines are increased while the levels of anti-inflammatory cytokines are decreased in AD patients. However, despite increasing data supporting the association between abnormal peripheral inflammation and AD, no well-established inflammatory biomarkers are currently available for AD. In this regards, we have studied an expanded spectrum of pro-inflammatory and anti-inflammatory cytokines and chemokines in the serum samples of the patients diagnosed with AD and compared them to those without cognitive impairment matched on age and gender.
Methods
We have simultaneously assayed cytokines and chemokines in the serum of AD patients (n=40) and normal controls (n=46) using MILLIPLEX Map Human Cytokine/Chemokine Magnetic Beas Panel on the Luminex xMAP technology according to the manufacturer’s protocol. The kit included the following 41 human cytokines and chemokines: EGF, IL-12P70, IL-13, IL-15, IL-17A, IL1RA, IP-10, MCP-1, MIP-1α, MIP-1β, RANTES, VEGF, FGF-2, TGF-α, FIT-3L, Fractalkine, GRO, MCP-3, MDC, PDGF-AA, PDGF-AB/BB, sCD40L, IL-1α, IL-1β, TNFα, G-CSF, IFNγ, TNFβ, IL-10, IL-2, GM-CSF, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, Eotaxin, IFNα2, and IL-12P40.
Results
We have found IL-12P40, IL-9, IL-7, GM-CSF, IL-10, IFNγ, IL-1α, MCP-3, FIT-3L, IL-17A, IL-13, IL-15, and IL-12P70 were significantly higher in Alzheimer’s patients compared to controls. At the same time, cognitively healthy controls had higher concentrations of PDGF-AB/BB, PDGF-AA, RANTES, and FGF-2 in the peripheral blood. We observed significant positive correlation between C-reactive protein and IP-10 (r=0.5), IL1RA (r=0.3), PDGF-AA (r=0.3), IL-10 (r=0.3), GRO (r=0.4), GCSF (r=0.3), PDGF-AB/BB (r=0.3).
Conclusion
Studying the expression levels of pro-inflammatory and anti-inflammatory cytokines and chemokines in the blood serum of Alzheimer’s dementia patients is of considerable interest since it can potentially contribute to the discovery of new blood-based biomarkers for earlier diagnosis of AD and development of the personalized treatment strategies.
1. Heneka M.T., Carson M.J., El Khoury J., Landreth G.E., Brosseron F., Feinstein D.L., Jacobs A.H., Wyss-Coray T., Vitorica J., Ransohoff R.M., Herrup K., Frautschy S.A., Finsen B., Brown G.C., Verkhratsky A., Yamanaka K., Koistinaho J., Latz E., Halle A., Petzold G.C., Town T., Morgan D., Shinohara M.L., Perry V.H., Holmes C., Bazan N.G., Brooks D.J., Hunot S., Joseph B., Deigendesch N., Garaschuk O., Boddeke E., Dinarello C.A., Breitner J.C., Cole G.M., Golenbock D.T., Kummer M.P. Neuroinflammation in Alzheimer's disease // The Lancet. Neurology. -2015. -Vol. 14. - 4. - P. 388-405.
2. Walker K.A., Ficek B.N., Westbrook R. Understanding the Role of Systemic Inflammation in Alzheimer’s Disease // ACS Chemical Neuroscience. -2019. -Vol. 10. - 8. - P. 3340-3342.
3. Xie J., Van Hoecke L., Vandenbroucke R.E. The Impact of Systemic Inflammation on Alzheimer’s Disease Pathology // Frontiers in Immunology. -2022. -Vol. 12.
4. Park J.C., Han S.H., Mook-Jung I. Peripheral inflammatory biomarkers in Alzheimer's disease: a brief review // BMB Rep. -2020. -Vol. 53. - 1. - P. 10-19.
| Original language | English |
|---|---|
| Number of pages | 1 |
| DOIs | |
| Publication status | Published - Dec 12 2022 |