In Vivo Imaging of Axonal Transport in Aging and Alzheimer΄s Disease.

In neurons, the process of axonal transport helps maintain health and homeostasis for normal neuronal functions. Protein products, synthesized in the cell body and organelles such as mitochondria, are transported via molecular ˵motors″ to the synapse for incorporation into membranes or cytoskeletal architecture, release into the synaptic cleft, or use in synaptic functioning. Retrograde transport occurs when substances, such as trophic factors, are taken up from the synaptic cleft via endocytosis and are transported back to the cell body to modulate further protein synthesis. Although retrograde transport is an important neuronal process, this chapter will focus on imaging of anterograde axonal transport and the effects of aging and neurodegeneration. Because axonal transport mechanisms become even more critical to maintain neuronal function in neuronal populations with long axonal projections, perturbations of axonal transport may contribute to the selective vulnerability of cortical projection neurons in neurodegenerative processes such as Alzheimer΄s disease (AD). With the increasing longevity of the world΄s population, aging and age-related diseases are becoming a major healthcare issue. Research in the areas of brain aging is critical, not only to maintaining life, but also to maintaining quality of life and sustaining a fully functional, independent, elderly population. Aging is also known to be a major risk factor for AD. According to pathological observations, cortical projection neurons are particularly vulnerable to AD pathophysiology (Hof et al., 1990). In such neurons, the process of axonal transport is particularly crucial to sustaining neuronal homeostasis and functions. Certain systems can be challenging to investigate non-invasively due to the relative inaccessibility of some brain regions and the technical challenges inherent in studying dynamic, sub-cellular processes. Therefore, the methodology to study axonal transport in living brains has been limited. This chapter will present on-going efforts to investigate this critical process using recently developed in vivo imaging techniques. [ABSTRACT FROM AUTHOR]