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Brain border-associated macrophages: common denominators in infection, aging, and Alzheimer's disease?
Sandro Da Mesquita1, Rejane Rua2
1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, USA.
Abstract:
Mammalian brain border-associated macrophages (BAMs) are strategically positioned to support vital properties and processes: for example, the composition of the brain's perivascular extracellular matrix and cerebrospinal fluid flow via the glymphatic pathway. BAMs also effectively restrict the spread of infectious microbes into the brain. However, while fighting infections, BAMs sustain long-term transcriptomic changes and can be replaced by inflammatory monocytes, potentially leading to a gradual loss of their beneficial homeostatic functions. We hypothesize that by expediting the deterioration of BAMs, multiple infection episodes might be associated with accelerated brain aging and the putative development of neurodegenerative diseases. Our viewpoint is supported by recent studies suggesting that rejuvenating aged BAMs, and counterbalancing their detrimental inflammatory signatures during infections, might hold promise in treating aging-related neurological disorders, including Alzheimer's disease (AD).
Insights
Repeated brain infections may accelerate brain aging and neurodegeneration by damaging border-associated macrophages (BAMs). Rejuvenating these immune cells could offer new treatments for Alzheimer's disease (AD) and other neurological disorders.
Area of Science:
- Neuroimmunology
- Brain Aging
- Neuroinflammation
Background:
- Border-associated macrophages (BAMs) are crucial for brain homeostasis, regulating the extracellular matrix and cerebrospinal fluid flow.
- BAMs protect the brain from infections but can undergo detrimental transcriptomic changes and be replaced by inflammatory monocytes after infection.
- These changes may impair BAMs' homeostatic functions, potentially contributing to brain aging and neurodegenerative diseases.
Purpose of the Study:
- To hypothesize the link between repeated infections, BAMs deterioration, and accelerated brain aging.
- To explore the potential of BAMs rejuvenation in mitigating age-related neurological disorders, including Alzheimer's disease.
Main Methods:
- Review of existing literature on BAMs function, immune response, and aging.
- Analysis of transcriptomic changes in BAMs during infection and aging.
- Consideration of therapeutic strategies targeting BAMs.
Main Results:
- Repeated infections may lead to long-term detrimental changes in BAMs.
- BAMs deterioration could accelerate brain aging and increase susceptibility to neurodegeneration.
- Rejuvenating aged BAMs and managing their inflammatory state shows therapeutic potential.
Conclusions:
- BAMs play a critical role in brain health and aging.
- Targeting BAMs may offer novel therapeutic avenues for age-related neurological diseases like Alzheimer's disease.
- Further research into BAMs' immune modulation is warranted for neuroprotection.
