Details

Autor(en) / Beteiligte

• Heuer, Sarah E.
• Bloss, Erik B.
• Howell, Gareth R.

Titel

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

Ist Teil von

• Neuropharmacology, 2024-08, Vol.254, p.109987, Article 109987

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2024

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• 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". •We review approaches used to investigate the role of microglia and neuronal synapse loss in aging and in AD.•We review key aspects of the interactions between microglia and neurons, with emphasis on changes at the synapse.•We discuss emerging technologies that could be used to understand these interactions during aging and in AD.•We also discuss new and emerging mouse models, including those that emphasize the importance of genetic diversity.