Microglial priming of antigen presentation and adaptive stimulation in Alzheimer’s disease
Open accessAbstract
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 imm…
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At least some plaque-associated microglia may borrow elements of lymphoid signaling logic rather than merely presenting antigen to lymphocytes.
“The recent finding therefore suggests that at least some plaque-associated microglia may borrow elements of lymphoid signaling logic rather than merely presenting antigen to lymphocytes [44,45,46].”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [44]
Microglia may act as local regulators of lymphocyte activation, particularly when blood-brain barrier dysfunction or chronic neuroinflammation allows greater immune-cell trafficking into the CNS.
“Reviews of microglia–lymphocyte communication have emphasized that microglia may act as local regulators of lymphocyte activation, particularly when blood–brain barrier dysfunction or chronic neuroinflammation allows greater immune-cell trafficking into the CNS.”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [44]
In inflammatory and neurodegenerative settings, microglia can upregulate antigen-presentation machinery, respond to interferon-γ and other lymphocyte-derived cytokines, and influence T-cell behavior within or near the central nervous system.
“In inflammatory and neurodegenerative settings, microglia can upregulate antigen-presentation machinery, respond to interferon-γ and other lymphocyte-derived cytokines, and influence T-cell behavior within or near the central nervous system.”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [44]
Microglia can express molecules associated with antigen presentation, including MHC class II-related genes and co-stimulatory ligands such as CD80 or CD86, especially under inflammatory conditions.
“They can express molecules associated with antigen presentation, including MHC class II–related genes and co-stimulatory ligands such as CD80 or CD86, especially under inflammatory conditions.”
From Lymphoid-like Suppressive Microglia in Alzheimer’s Disease: A New Neuroimmune Regulatory Axis? (2026) · cites this paper as [44]
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Autophagy & Phagocytosis in Neurological Disorders and their Possible Cross-talk
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Mechanistic role and potential of Ayurvedic herbs as anti-aging therapies
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Chidambaram, H., & Chinnathambi, S. (2025) · Brain Network Disorders · doi:10.1016/j.bnd.2024.12.005 · Cited by 25 · see citing works
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Pathogenesis of miR-155 on nonmodifiable and modifiable risk factors in Alzheimer’s disease
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G-protein coupled receptors regulates Tauopathy in neurodegeneration
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Neuroimmune multi-hit perspective of coronaviral infection
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A glance through the effects of CD4 + T cells, CD8 + T cells, and cytokines on Alzheimer's disease
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Tau protein structure and dynamics
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Self-citationTau and Amyloid beta causes microglial activation in Alzheimer’s disease
Chinnathambi, S., Adithyan, A., Chandrashekar, M., & Rangappa, N. (2025) · Advances in clinical chemistry · doi:10.1016/bs.acc.2025.06.002 · Cited by 18 · see citing works
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HMGB1 is a Potential and Challenging Therapeutic Target for Parkinson’s Disease
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The immunomodulatory effect of microglia on ECM neuroinflammation via the PD‐1/PD‐L1 pathway
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Intermittent hypoxia treatments cause cellular priming in human microglia
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Mechanisms and routes of G-protein coupled receptor-mediated Tau degradation in Alzheimer’s disease
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Self-citationMicroglial Uptake of Extracellular Tau by Actin-Mediated Phagocytosis
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Self-citationTranscriptomic analysis reveals sex-specific patterns in the hippocampus in Alzheimer’s disease
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Internalization of extracellular Tau oligomers in Alzheimer’s disease
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Self-citationPhotodynamic treatment modulates various GTPase and cellular signalling pathways in Tauopathy
Dubey, T., & Chinnathambi, S. (2021) · Small GTPases · doi:10.1080/21541248.2021.1940722 · Cited by 13 · see citing works
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α-Linolenic acid modulates phagocytosis of extracellular Tau and induces microglial migrationPreprint
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Self-citationLipid role in synapse and nuclear envelope-associated endocytic pathways in Tauopathy
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Self-citationT Cells Trafficking into the Brain in Aging and Alzheimer’s Disease
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Ageing-related changes in the regulation of microglia and their interaction with neurons
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Tailoring MAPK Pathways: New Therapeutic Avenues for Treating Alzheimer’s Disease
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Histone deacetylase’s regulates Tau function in Alzheimer’s disease
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Tau PET probes for Alzheimer’s disease detection and their structural characterization
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Self-citationCrosstalk between peripheral immunity and central nervous system in Alzheimer’s disease
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Tau proteotasis in Alzheimer’s disease
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Cholesterol metabolism regulates Tauopathy in Alzheimer’s disease
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Aging Microglia and Their Impact in the Nervous System
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ADVANCEMENT IN THE TREATMENT OF ALZHEIMER'S DISEASE, 2023
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Medicinal chemistry-based novel herapeutics for Tauopathies in Alzheimer’s disease
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Self-citationUnderstanding the impact of cytoskeleton disruption on synaptic plasticity in Alzheimer’s disease
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- Authors
- Das, R., & Chinnathambi, S.
- Affiliations
- National Chemical Laboratory (IN)
- Corresponding author
- Chinnathambi, Subashchandrabose
- Venue
- Cellular and Molecular Life Sciences
- Published
- 2019-05-15
- Volume
- 76
- Issue
- 19
- Pages
- 3681-3694
- ISSN
- 1420-682X (ISSN-L)
- 1420-9071
- PMC
- PMC11105582
- OpenAlex
- W2945276138
- Cited by
- 147
- References
- 149
- Citations by year
- 2026: 18 · 2025: 28 · 2024: 24 · 2023: 22 · 2022: 8 · 2021: 29 · 2020: 16 · 2019: 1 · 2018: 1
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Cellular and Molecular Life Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Department of Biotechnology , Ministry of Science and Technology (DBT-HDDB)- BT/PR/15780/MED/122/4/2016)
- Council of Scientific and Industrial Research (CSIR NCL MLP 029526)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
- Keywords
- Alzheimer's disease, microglia, antigen presentation, neuroinflammation, amyloid-beta, tau protein, CD4+ T cells, M1/M2 microglial polarization, neuroprotection, astroglia, lysosomal processing, immunotherapy
- MeSH terms
- Alzheimer Disease, Brain, Humans, Immunotherapy, T-Lymphocytes, Neuroimmunomodulation, Protein Folding, Microglia, Antigen Presentation, Adaptive Immunity
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