Microglia in Aging and Alzheimer’s Disease: A Comparative Species Review
Open Access
- 8 May 2021
- Vol. 10 (5), 1138
- https://doi.org/10.3390/cells10051138
Abstract
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.Funding Information
- National Institutes of Health (R01ES026057, R01ES021800, R01ES024288-03S1, U01NS108956)
- National Institute on Aging (R01AG067419)
This publication has 323 references indexed in Scilit:
- Neuroinflammation and Neuronal Loss Precede Aβ Plaque Deposition in the hAPP-J20 Mouse Model of Alzheimer’s DiseasePLOS ONE, 2013
- Age related changes in microglial phenotype vary between CNS regions: Grey versus white matter differencesBrain, Behavior, and Immunity, 2012
- Effects of aging and sensory loss on glial cells in mouse visual and auditory corticesGlia, 2012
- National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease: a practical approachActa Neuropathologica, 2011
- Reactive Glia not only Associates with Plaques but also Parallels Tangles in Alzheimer's DiseaseThe American Journal of Pathology, 2011
- Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s diseaseActa Neuropathologica, 2009
- Central inhibition of interleukin-1β ameliorates sickness behavior in aged miceBrain, Behavior, and Immunity, 2009
- Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1β and anti-inflammatory IL-10 cytokinesBrain, Behavior, and Immunity, 2009
- Time course of hippocampal IL-1 β and memory consolidation impairments in aging rats following peripheral infectionBrain, Behavior, and Immunity, 2009
- Tauopathy with paired helical filaments in an aged chimpanzeeJournal of Comparative Neurology, 2008