Strategies to dissect microglia-synaptic interactions during aging and in Alzheimer's disease.

Document Type

Article

Publication Date

8-15-2024

Keywords

JMG, Animals, Humans, Aging, Alzheimer Disease, Brain, Microglia, Neuronal Plasticity, Synapses

JAX Source

Neuropharmacology. 2024;254:109987.

ISSN

1873-7064

PMID

38705570

DOI

https://doi.org/10.1016/j.neuropharm.2024.109987

Grant

E.B.B is supported by the Jackson Laboratory and R01AG079877. G. R.H. is supported by AG054345, AG083891, and the Diana Davis Spencer Foundation.

Abstract

Age is the largest risk factor for developing Alzheimer's disease (AD), a neurodegenerative disorder that causes a progressive and severe dementia. The underlying cause of cognitive deficits seen in AD is thought to be the disconnection of neural circuits that control memory and executive functions. Insight into the mechanisms by which AD diverges from normal aging will require identifying precisely which cellular events are driven by aging and which are impacted by AD-related pathologies. Since microglia, the brain-resident macrophages, are known to have critical roles in the formation and maintenance of neural circuits through synaptic pruning, they are well-positioned to modulate synaptic connectivity in circuits sensitive to aging or AD. In this review, we provide an overview of the current state of the field and on emerging technologies being employed to elucidate microglia-synaptic interactions in aging and AD. We also discuss the importance of leveraging genetic diversity to study how these interactions are shaped across more realistic contexts. We propose that these approaches will be essential to define specific aging- and disease-relevant trajectories for more personalized therapeutics aimed at reducing the effects of age or AD pathologies on the brain. This article is part of the Special Issue on "Microglia".

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