Cellular and Molecular Life Sciences

, Volume 76, Issue 19, pp 3681–3694 | Cite as

Microglial priming of antigen presentation and adaptive stimulation in Alzheimer’s disease

  • Rashmi Das
  • Subashchandrabose ChinnathambiEmail author


The prominent pathological consequences of Alzheimer’s disease (AD) are the misfolding and mis-sorting of two cellular proteins, amyloid-β and microtubule-associated protein Tau. The accumulation of toxic phosphorylated Tau inside the neurons induces the increased processing of amyloid-β-associated signaling cascade and vice versa. Neuroinflammation-driven synaptic depletion and cognitive decline are substantiated by the cross talk of activated microglia and astroglia, leading to neuron degeneration. Microglia are the brain-resident immune effectors that prove their diverse functions in maintaining CNS homeostasis via collaboration with astrocytes and T lymphocytes. Age-related senescence and chronic inflammation activate microglia with increased pro-inflammatory markers, oxidative damage and phagocytosis. But the improper processing of misfolded protein via lysosomal pathway destines the spreading of ‘seed’ constituents to the nearby healthy neurons. Primed microglia process and present self-antigen such as amyloid-β and modified Tau to the infiltrated T lymphocytes through MHC I/II molecules. After an effective conversation with CD4+ T cells, microglial phenotype can be altered from pro-active M1 to neuro-protective M2 type, which corresponds to the tissue remodeling and homeostasis. In this review, we are focusing on the change in functionality of microglia from innate to adaptive immune response in the context of neuroprotection, which may help in the search of novel immune therapy in AD.


Microglia Antigen presentation Neuroimmunomodulation T cell infiltration Immunotherapy Tauopathy Alzheimer’s disease 



Beta secretase 1


Post-translational modifications


Blood–brain barrier


Central nervous system


Reactive oxygen species


Nitric oxide


Inorganic nitric oxide synthase


Cluster of differentiation


Major histocompatibility complex


Transforming growth factor β


Tumor necrosis factor α






Helper T cell


Regulatory T cell




Complement receptor


Nuclear factor κ for B cell


Mammalian target for rapamycin


Protein kinase B


Adenosine tri-phosphate


Antigen-presenting cell


Triggering receptor expressed on myeloid cells 2


Apolipoprotein E


Nuclear factor kappa-light-chain-enhancer of activated B cells


p38-mitogen-activated protein kinases


Colony-stimulating factor-1 receptor



This project is supported in part by grants from the Department of Biotechnology, Neuroscience Task Force (Medical Biotechnology-Human Development & Disease Biology DBT-HDDB)-BT/PR/15780/MED/122/4/2016 and in-house CSIR-National Chemical Laboratory Grant MLP029526. Special thanks to Ms. Nalini Gorantla, Mr. Abhishek Balmik and Ms. Shweta Sonawane for proofreading the manuscript. Rashmi Das acknowledges the fellowship from University Grant Commission (UGC) India.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Neurobiology Group, Division of Biochemical SciencesCSIR-National Chemical LaboratoryPuneIndia
  2. 2.Academy of Scientific and Innovative Research (AcSIR)PuneIndia

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