4.6 Review

Microglia in Aging and Alzheimer's Disease: A Comparative Species Review

Journal

CELLS
Volume 10, Issue 5, Pages -

Publisher

MDPI
DOI: 10.3390/cells10051138

Keywords

microglia; neuroinflammation; aging; Alzheimer’ s disease; primate; rodent

Categories

Funding

  1. National Institutes of Health [R01ES026057, R01ES021800, R01ES024288-03S1, U01NS108956]
  2. National Institute on Aging [R01AG067419]

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Microglia play crucial roles in neuroinflammation, undergoing rapid changes and impacting the brain's susceptibility to neurodegenerative diseases during infection, trauma, and aging. Despite advances in the field, drug treatment success rates for age-related and neurodegenerative diseases remain low, potentially due to issues in translating findings from animal models to clinical settings.
Microglia are the primary immune cells of the central nervous system that help nourish and support neurons, clear debris, and respond to foreign stimuli. Greatly impacted by their environment, microglia go through rapid changes in cell shape, gene expression, and functional behavior during states of infection, trauma, and neurodegeneration. Aging also has a profound effect on microglia, leading to chronic inflammation and an increase in the brain's susceptibility to neurodegenerative processes that occur in Alzheimer's disease. Despite the scientific community's growing knowledge in the field of neuroinflammation, the overall success rate of drug treatment for age-related and neurodegenerative diseases remains incredibly low. Potential reasons for the lack of translation from animal models to the clinic include the use of a single species model, an assumption of similarity in humans, and ignoring contradictory data or information from other species. To aid in the selection of validated and predictive animal models and to bridge the translational gap, this review evaluates similarities and differences among species in microglial activation and density, morphology and phenotype, cytokine expression, phagocytosis, and production of oxidative species in aging and Alzheimer's disease.

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