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Aging and disease    2020, Vol. 11 Issue (6) : 1594-1607     DOI: 10.14336/AD.2020.0205
Review Article |
A Perspective on Roles Played by Immunosenescence in the Pathobiology of Alzheimer's Disease
Yan Zhao, Jun-Kun Zhan, Youshuo Liu
Department of Geriatrics, Institute of Aging and Geriatrics, the Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China
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Alzheimer's disease (AD) is a chronic progressive neurodegenerative disorder. Aging is the most significant risk factor for late-onset AD. The age-associated changes in the immune system are termed immunosenescence. A close connection between immunosenescence and AD is increasingly recognized. This article provides an overview of immunosenescence and evidence for its role in the pathogenesis of AD and possible mechanisms as well as the outlook for drug development.

Keywords immunosenescence      Alzheimer’s disease      inflammation      aging     
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These authors contributed equally to this work.

Just Accepted Date: 13 February 2020   Issue Date: 19 November 2020
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Zhao Yan
Zhan Jun-Kun
Liu Youshuo
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Zhao Yan,Zhan Jun-Kun,Liu Youshuo. A Perspective on Roles Played by Immunosenescence in the Pathobiology of Alzheimer's Disease[J]. Aging and disease, 2020, 11(6): 1594-1607.
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Immune cells or their productsChanges related to AD pathologyRef.
Innate immunity
MicrogliaAbility to phagocytose Aβ fibrils ↓[71]
Production of proinflammatory cytokines ↑[72,73]
Monocyte/MacrophageFunctional proinflammatory response ↓[69]
Phagocytosis and chemotaxis ↓[78]
The imbalance between M1 and M2 ↑[83]
Natural killer cellsNumber of NK cells and cytotoxic activity ↓[88]
Adaptive immunity
T cells
Th1/IFNγIFNγ signaling activation supports neural circuits ↓[93]
Th2/IL-4IL-4 stimulates astrocytes to produce BDNF ↓[94]
Treg cellsFrequency of Treg cells ↑[98]
B cellsAntibody specificity and affinity ↓[103]
Aβ antibody levels ↓[108]
Table 1  Alterations in the cellular components of innate and adaptive immunity associated with aging.
Figure 1.  Schematic representation of age-related changes of immune barriers. Studies have shown that changes in immune barriers such as permeability and receptor expression, increasing challenges of the innate immune system, which are associated with the pathology of AD. Selective trafficking of immune cells via the immune barrier is also one of the underlying mechanisms of pathological changes in neurodegenerative diseases.
Figure 2.  A close connection between immunosenescence and AD is increasingly recognized. New treatments for AD aiming at regulating immunosenescence may relieve neurodegeneration. As to the imbalance of barrier flora, chronic low-grade inflammation and aging, antibacterial, antiviral and anti-inflammatory treatment, immunotherapy, and anti-aging strategy may become new methods to treat AD.
Drug classificationagentMechanism of actionRef.
Antimicrobial therapyAntibiotic treatmentAvoid bacterial infections[122]
Antiviral agentProtects against virus infections[125,126]
GV-971Regulate gut flora imbalance and
reshape immune homeostasis
Anti-inflammatory treatmentAnti-inflammatory drugsModulate inflammatory processes[128]
ImmunotherapyAntiamyloid agentsRemove amyloid and prevent amyloid production and aggregation[131]
Anti-tau agentsReduce tau-mediated neuronal damage[131]
immunomodulatorscytokines, complement components, and histocompatibility proteinsImprove cell signaling[132]
Anti-aging strategyGeroprotectorsSlow the rate of biological aging[134]
Young bloodModulate aging and rejuvenate organs[135,136]
Inhibition of mTORImprove vaccine response[137]
Table 2  Novel treatments for AD to reverse immunosenescence.
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