Abstract
Extensive human studies and animal models show that chronic immune system stimulation involving microglia, inflammasome, complement activation, synthesis of cytokines, and reactive oxygen species exacerbates neurodegeneration in Alzheimer’s disease (AD) and other tauopathies. Abnormalities in tau, Aβ, and microglial activation are frequently observed in dementia patients and indicate that these elements may work in concert to cause cognitive impairment. Contradicting reports from postmortem studies demonstrating the presence of Aβ aggregates in the brains of cognitively healthy individuals, as well as other investigations, show that tau aggregation is more strongly associated with synapse loss, neurodegeneration, and cognitive decline than amyloid pathology. Tau association with microtubules’ surface promotes their growth and maintains their assembly, dynamicity, and stability. In contrast, the reduced affinity of hyperphosphorylated and mislocalized tau to microtubules leads to axonal deficits and neurofibrillary tangles (NFTs). Loss of microglial neuroprotective and phagocytic functions, as indicated by the faulty clearance of amyloid plaques, as well as correlations between microglial activation and tau tangle spread, all demonstrate the critical involvement of malfunctioning microglia in driving tau propagation. This review discusses the recent reports on the contribution of microglial cells to the development and progression of tau pathology. The detailed study of pathogenic mechanisms involved in interactions between neuroinflammation and tau spread is critical in identifying the targets for efficacious treatment strategies in AD.
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Author contributions: Gunel Ayyubova has entirely done all work related to this manuscript.
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Research funding: None declared.
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Conflict of interest statement: No conflicts of interest regarding this article to be declared.
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Ethical approval: Not applicable.
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Informed consent statement: Not applicable.
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