In this installment of the Donders Beauty of the Brain Series, we present a captivating image of a cultured hippocampal slice from a mouse brain used to examine what happens at an early stage of Alzheimer’s Disease.

The magenta color highlights microglia, the brain’s local immune cells that act as the first line of defense against infection and injury. These cells also play a role in maintaining brain health by clearing away damaged cells and debris. The green and red colors represent inhibitory and excitatory synapses, respectively. Synapses are the communication points between neurons, with inhibitory synapses reducing neuronal activity and excitatory synapses increasing it.

It is well known that the level of the harmful protein Amyloid-beta (Aβ), which accumulates in the brains of Alzheimer’s patients and disrupts neuronal function, is elevated even before cognitive problems occur. In a previous study (https://pubmed.ncbi.nlm.nih.gov/33074225/ ), Ruiter et al demonstrated that inhibitory synapses are especially susceptible to damage caused by Aβ. This suggests that as Aβ builds up in the brain, it may preferentially harm inhibitory synapses, leading to their loss. As a result, the delicate balance between inhibitory and excitatory neuronal activity could be disrupted, potentially contributing to the neuronal dysfunction seen in Alzheimer’s Disease.

Microglia, pictured in magenta, have been shown to play a crucial role in Alzheimer’s Disease. However, it is not entirely clear if their contribution is mostly positive, such as clearing away harmful Aβ proteins, or negative, such as inadvertently damaging synapses in the process. The current study aims to clarify whether microglia react to synaptic damage caused by Aβ in an attempt to repair or clear away the damage, or whether the actions of microglia themselves might unintentionally contribute to the synaptic impairments observed in Alzheimer’s Disease.

Images and research courtesy of Alexandra Olander and Corette Wierenga.