Journal of Brain and Neurology

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Opinion Article - Journal of Brain and Neurology (2023) Volume 6, Issue 4

Role of microglia in early and intermediate stages of Alzheimer′s disease

Curran Smith*

Department of Medicine

*Corresponding Author:
Curran Smith
Department of Medicine
Technical University of Munich
Germany
E-mail: currans@tum.de

Received:28-Jun-2023, Manuscript No. AAJBN-23-105465; Editor assigned:30-Jun-2023, PreQC No. AAJBN-23-105465 (PQ); Reviewed:14-Jul-2023, QC No. AAJBN-23-105465; Revised:18-Jul-2023, Manuscript No. AAJBN-23-105465 (R); Published:25-Jul-2023, DOI:10.35841/ aajbn-6.4.152

Citation: Smith C. Role of microglia in early and intermediate stages of Alzheimer’s disease. J Brain Neurol. 2023;6(4):152

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Introduction

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the progressive decline of cognitive function, memory loss, and behavioral changes. While the exact cause of Alzheimer's remains elusive, researchers have increasingly focused on the role of microglia, the brain's resident immune cells, in the development and progression of this devastating condition. This article aims to explore the involvement of microglia in the early and intermediate stages of Alzheimer's disease and shed light on their complex and multifaceted role in the disease pathology. Microglias are specialized immune cells that play a crucial role in maintaining the brain's homeostasis and protecting it against infections, injury, and toxins. In response to any brain injury or disease, microglia become activated and undergoes morphological and functional changes. In Alzheimer's disease, microglia activation is observed early on, leading to a state of chronic neuroinflammation. This neuroinflammation is characterized by the release of pro-inflammatory molecules, such as cytokines and chemokine’s, which can contribute to neuronal damage [1].

Microglial Dysfunction in Early Stages

During the early stages of Alzheimer's disease, microglia display both beneficial and detrimental effects. Initially, microglia attempt to clear accumulated amyloid-beta (Aβ) plaques, one of the hallmarks of AD, through a process called phagocytosis. However, in the Alzheimer's brain, microglia often fails to efficiently clear these plaques, leading to their persistence and the formation of toxic aggregates. This impaired phagocytic function of microglia is thought to be influenced by genetic factors environmental cues and age-related changes in microglial activity [2].

Role of Microglia in Intermediate Stages

As Alzheimer's disease progresses to the intermediate stages, microglia continues to contribute to the disease pathology. Research suggests that microglia become increasingly reactive and adopts a dysfunctional phenotype. These activated microglia release excessive amounts of pro-inflammatory molecules, amplifying the neuroinflammatory response. This chronic inflammation can lead to synaptic dysfunction, neuronal death, and contribute to the cognitive decline observed in Alzheimer's patients [3].

Apart from amyloid plaques, another hallmark of Alzheimer's disease is the accumulation of hyperphosphorylated tau protein, leading to the formation of neurofibrillary tangles. Recent studies have highlighted the involvement of microglia in tau pathology. Activated microglia can release toxic factors that induce tau phosphorylation and propagation, further exacerbating neurodegeneration in Alzheimer's disease. Understanding the complex role of microglia in Alzheimer's disease has prompted the exploration of therapeutic strategies that target these immune cells. One approach involves modulating microglial activity to restore their phagocytic function and enhance the clearance of Aβ plaques. Additionally, targeting the pro-inflammatory signaling pathways in microglia is being investigated as a means to reduce chronic neuroinflammation. However, developing effective therapies requires a comprehensive understanding of the diverse functions of microglia and their interplay with other cell types in the brain.

Microglial Activation and Neurotoxicity

In addition to their involvement in neuroinflammation and clearance of amyloid plaques, microglia also has the potential to exert neurotoxic effects in Alzheimer's disease. When overactivated or exposed to chronic neuroinflammatory stimuli, microglia can release an array of cytotoxic molecules, including reactive oxygen species (ROS), nitric oxide (NO), and pro-inflammatory cytokines. These neurotoxic factors can damage neurons and disrupt synaptic connections, contributing to the progressive cognitive decline observed in Alzheimer's patients. Moreover, microglial activation in response to chronic inflammation can trigger a phenomenon known as "bystander damage." In this process, microglia release inflammatory mediators that lead to the activation of neighboring microglia and perpetuate a cycle of neuroinflammation and neuronal damage. This amplification of inflammatory signals further exacerbates the pathological cascade in Alzheimer's disease. Recent studies have highlighted the remarkable heterogeneity of microglia, suggesting that different subsets of microglia may adopt distinct roles in Alzheimer's disease. It is now recognized that microglia can exhibit a spectrum of activation states, ranging from a neuroprotective phenotype to a neurotoxic phenotype. These different phenotypes are characterized by distinct gene expression profiles and functional properties. Understanding this microglial heterogeneity is crucial for developing targeted therapies that can selectively modulate specific microglial subsets to promote neuroprotection while minimizing neurotoxicity [4].

Genetic factors play a significant role in the susceptibility and progression of Alzheimer's disease. Variations in genes associated with microglial function and immune response have been implicated in disease risk. For instance, variants of the triggering receptor expressed on myeloid cells 2 (TREM2) gene have been associated with an increased risk of Alzheimer's disease. TREM2 is expressed on the surface of microglia and plays a role in regulating their phagocytic function and inflammatory responses. Dysfunction of TREM2 can impair microglial clearance of amyloid plaques and contribute to disease progression. Given the complex and multifaceted role of microglia in Alzheimer's disease, targeting microglial function represents a potential therapeutic approach. Several strategies are being explored to modulate microglial activity and neuroinflammation in Alzheimer's disease. This includes the development of small molecules or antibodies that can selectively enhance microglial phagocytosis of amyloid plaques and reduce neurotoxicity. Other approaches aim to promote a shift in microglial phenotype from a pro-inflammatory state to an anti-inflammatory or neuroprotective state [5].

Conclusion

Microglia, the immune cells of the brain, plays a complex and multifaceted role in the early and intermediate stages of Alzheimer's disease. While their initial response aims to clear amyloid plaques and maintain brain homeostasis, dysregulation of microglial activation and chronic neuroinflammation can contribute to neurotoxicity and neuronal damage. Understanding the intricacies of microglial function, heterogeneity, and their interaction with genetic factors is crucial for developing effective therapeutic interventions that harness the potential of microglia for neuroprotection in Alzheimer's disease. Further research is needed to elucidate the precise mechanisms underlying microglial dysfunction and identify novel targets for intervention, bringing hope for future treatments that can slow or halt the progression of this devastating neurodegenerative disorder.

References

  1. Ramanan VK, Risacher SL, Nho K, et al. GWAS of longitudinal amyloid accumulation on 18F-florbetapir PET in Alzheimer’s disease implicates microglial activation gene IL1RAP. Brain. 2015;138(10):3076-88.

    2. Indexed at, Google Scholar, Cross Ref

  2. Ransohoff RM, Perry VH. Microglial physiology: unique stimuli, specialized responses. Annu Rev Immunol. 2009;27:119-45.

    3. Indexed at, Google Scholar, Cross Ref

  3. Rebeck GW, Reiter JS, Strickland DK, et al. Apolipoprotein E in sporadic Alzheimer's disease: allelic variation and receptor interactions . Neuron. 1993;11(4):575-80

    4. Indexed at, Google Scholar, Cross Ref

  4. Reiman EM, Chen K, Liu X, et al. Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease . Proc Natl Acad Sci. 2009;106(16):6820-5.

    5. Indexed at, Google Scholar, Cross Ref

  5. Rosen AM, Stevens B. The role of the classical complement cascade in synapse loss during development and glaucoma . Adv Exp Med Biol. 2010:75-93.

    6. Indexed at, Google Scholar, Cross Ref

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