In Vivo Imaging Biomarkers in Mouse Models of Alzheimer's Disease: Are We Lost in Translation or Breaking Through?

Figure 1

Summary of imaging techniques. This figure schematizes the principal methodologies and tools that can be used to image in vivo the brain lesions and functional alterations developed by mouse models of AD. Radioligands analyzed by PET (green dots) can be used to map brain metabolic deficits in APP(xPS1) transgenic mice. Their relevance for plaque detection in mouse models is more controversial. Applications derived from small animal MR-based imaging techniques (red dots) are more versatile. MRI allows the detection of pathological markers at the regional level (e.g., evaluation of brain atrophy) and also at a microscopic resolution (e.g., visualization of amyloid plaques). In vivo MRI is also a tool to assess functional markers of the pathology such as anomalies in brain perfusion. The recent development of manganese-enhanced MRI has opened new opportunities to map in vivo brain connectivity and neuronal activity with an exquisite spatial resolution. The detection of discrete markers at the (sub)cellular level relies today on the use of high resolution, but also more invasive, imaging techniques that require direct access to brain tissues through a craniotomy in anaesthetized animals: with multiphoton microscopy (blue dots) it is for instance possible to detect intraneuronal neurofibrillary tangles as well as dystrophic neurites in APP(xPS1) transgenic mice.