Chapter 7 - Detection of amyloid aggregation in living systems

Abstract

With the current recognition that amyloidogenic proteins can aggregate into species that induce (neuro)degenerative processes, it becomes crucial to obtain insight into how these processes are regulated by the cell. This realization triggered many researchers worldwide into investigating the behavior of aggregating amyloidogenic proteins in test tubes, cell cultures, or ex vivo. However, information on the aggregation of such proteins within their complex environment of a living animal is less available. Limiting factors are the availability of suitable imaging techniques, labeling or other means of specifically recognizing the aggregating species of interest, and the challenge of imaging such processes in living organisms. This chapter discusses currently available methodology, based on Förster resonance energy transfer and fluorescence lifetime imaging, bioluminescence detection, in vivo microdialysis, positron emission tomography, and the use of optical fibers and cranial windows to obtain insight into amyloid aggregation in living systems. This chapter also highlights the suitability, possibilities, and limitations of a number of model organisms that are commonly used in in vivo amyloid aggregation studies, including Caenorhabditis elegans and zebrafish as well as transgenic mice. Last, this chapter will highlight what has been learned from living system amyloid studies and sheds some light onto future perspectives in terms of technology development.