Cellular and Molecular Life Sciences

, Volume 75, Issue 17, pp 3099–3120 | Cite as

The potential importance of myeloid-derived suppressor cells (MDSCs) in the pathogenesis of Alzheimer’s disease

  • Antero Salminen
  • Kai Kaarniranta
  • Anu Kauppinen


The exact cause of Alzheimer’s disease (AD) is still unknown, but the deposition of amyloid-β (Aβ) plaques and chronic inflammation indicates that immune disturbances are involved in AD pathogenesis. Recent genetic studies have revealed that many candidate genes are expressed in both microglia and myeloid cells which infiltrate into the AD brains. Invading myeloid cells controls the functions of resident microglia in pathological conditions, such as AD pathology. AD is a neurologic disease with inflammatory component where the immune system is not able to eliminate the perpetrator, while, concurrently, it should prevent neuronal injuries induced by inflammation. Recent studies have indicated that AD brains are an immunosuppressive microenvironment, e.g., microglial cells are hyporesponsive to Aβ deposits and anti-inflammatory cytokines enhance Aβ deposition. Immunosuppression is a common element in pathological disorders involving chronic inflammation. Studies on cancer-associated inflammation have demonstrated that myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of tumor cells. Immunosuppression is not limited to tumors, since MDSCs can be recruited into chronically inflamed tissues where inflammatory mediators enhance the proliferation and activation of MDSCs. AD brains express a range of chemokines and cytokines which could recruit and expand MDSCs in inflamed AD brains and thus generate an immunosuppressive microenvironment. Several neuroinflammatory disorders, e.g., the early phase of AD pathology, have been associated with an increase in the level of circulating MDSCs. We will elucidate the immunosuppressive armament of MDSCs and present evidences in support of the crucial role of MDSCs in the pathogenesis of AD.


Aging Alzheimer Hypoxia Neuroinflammation NF-κB Senescence 




Alzheimer’s disease


Amyloid precursor protein


Arginase 1


Regulatory B cell


Cerebral amyloid angiopathy


CCAAT/enhancer-binding protein β


C/EBP-homologous protein


Forkhead box P3


General control nonderepressible 2 kinase


Hypoxia-inducible factor-1α


High mobility group box 1


Herpes simplex virus type 1


Indoleamine-pyrrole 2,3-dioxygenase


Mild cognitive impairment


Myeloid-derived suppressor cell


Macrophage migration inhibitory factor


Nuclear factor-κB


Nitric oxide


Nitric oxide synthase


NADPH2 oxidase 2


Nuclear factor-erythroid 2-related factor 2


Non-steroidal anti-inflammatory drug


Programmed death-ligand 1


Prostaglandin E2


Signal transducer and activator of transcription


Transforming growth factor-β


Tumor necrosis factor-α


Regulatory T cell


Triggering receptor expressed on myeloid cells 2



This study was financially supported by the Grants from the Terveyden Tutkimuksen Toimikunta of Academy of Finland (AK297267, AK307341, and KK296840), the Kuopio University Hospital VTR Grant (KK5503743), the Emil Aaltonen Foundation, the Finnish Cultural Foundation, and the Finnish Eye Foundation. The authors thank Dr. Ewen MacDonald for checking the language of the manuscript.

Compliance with ethical standards

Conflict of interest

The authors state that there are no personal or institutional conflicts of interest.


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Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Antero Salminen
    • 1
  • Kai Kaarniranta
    • 2
    • 3
  • Anu Kauppinen
    • 4
  1. 1.Department of Neurology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  2. 2.Department of Ophthalmology, Institute of Clinical MedicineUniversity of Eastern FinlandKuopioFinland
  3. 3.Department of OphthalmologyKuopio University HospitalKuopioFinland
  4. 4.School of Pharmacy, Faculty of Health SciencesUniversity of Eastern FinlandKuopioFinland

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