Investigating the influence of astrocytes on functional network disruptions and amyloid pathology at early disease stages in a mouse model of Alzheimer's disease

Alzheimer’s disease (AD) is the most common type of dementia in the elderly population. There are symptomatic treatments that can delay further symptom progression, but currently there is no cure. Efficient treatment development requires a) knowledge on early mechanisms during AD progression and b) tools that allow follow up of disease and treatment effects in a clinically translational way. AD pathology includes the formation of toxic soluble amyloid beta (Aβ) peptides that aggregate to plaques, followed by tau pathology and neuronal loss. Studies in mouse models show that astrocytes are disrupted before Aβ plaques deposition, possibly leading to brain function deficits. In this project we will apply a powerful combination of techniques in a mouse model of Aβ pathology to evaluate brain function at different scales. Firstly, we will use functional MRI to study functional network in the brain. This imaging method is used routinely in human AD research, facilitating translation of our findings to clinical settings. Secondly, we will use two-photon microscopy and cell type-specific modulations to investigate the contribution of astrocytes to a) the disruptions of brain functional networks measured with MRI and b) to disease progression. This will provide insight into disease mechanisms and potential targets for treatment development. By using the combination of these techniques we aim to bridge the gap between fundamental and translational research.