Microglial pathology
Abstract:
This paper summarizes pathological changes that affect microglial cells in the human brain during aging and in aging-related neurodegenerative diseases, primarily Alzheimer's disease (AD). It also provides examples of microglial changes that have been observed in laboratory animals during aging and in some experimentally induced lesions and disease models. Dissimilarities and similarities between humans and rodents are discussed in an attempt to generate a current understanding of microglial pathology and its significance during aging and in the pathogenesis of Alzheimer dementia (AD). The identification of dystrophic (senescent) microglia has created an ostensible conflict with prior work claiming a role for activated microglia and neuroinflammation during normal aging and in AD, and this has raised a basic question: does the brain's immune system become hyperactive (inflamed) or does it become weakened (senescent) in elderly and demented people, and what is the impact on neuronal function and cognition? Here we strive to reconcile these seemingly contradictory notions by arguing that both low-grade neuroinflammation and microglial senescence are the result of aging-associated free radical injury. Both processes are damaging for microglia as they synergistically exhaust this essential cell population to the point where the brain's immune system is effete and unable to support neuronal function.
Insights
Aging brains show both inflammation and senescence in microglial cells, the brain's immune cells. This dual decline, driven by free radical damage, impairs immune function and impacts cognition in aging and Alzheimer's disease.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Microglial cells are key immune cells in the brain.
- Aging and neurodegenerative diseases like Alzheimer's disease (AD) involve microglial changes.
- Conflicting evidence exists regarding whether microglia become hyperactive (neuroinflammation) or weakened (senescence) with age.
Purpose of the Study:
- To summarize microglial pathological changes in human aging and AD.
- To compare human and rodent microglial changes during aging and disease.
- To reconcile the concepts of neuroinflammation and microglial senescence in aging and AD.
Main Methods:
- Review of pathological changes in human and animal models.
- Comparison of microglial alterations in humans versus rodents.
- Analysis of the impact of aging-associated free radical injury on microglia.
Main Results:
- Microglial cells exhibit both senescence (dystrophic changes) and low-grade neuroinflammation during aging and AD.
- Both processes stem from aging-associated free radical injury.
- These combined effects exhaust microglia, leading to an impaired brain immune system.
Conclusions:
- Microglial senescence and neuroinflammation are not contradictory but are synergistic consequences of aging.
- This synergistic damage weakens the brain's immune system, compromising neuronal function and cognition.
- Understanding these dual microglial pathologies is crucial for addressing aging-related cognitive decline and AD pathogenesis.
