Nanometer resolution imaging and tracking of axonal cargo transport in normal and degenerative neurons

Survival and function of neurons depend critically on bidirectional active transport of essential cargoes along axonal microtubules. Transport defects have been strongly implicated in many human neurodegenerative diseases such as Alzheimer´s disease. To study related physiology and disease mechanisms, we developed methods to image and automatically track individual cargoes at nanometer resolution. Using these tools, we characterized and compared transport behavior in normal neurons and degenerative neurons in a Drosophila model of Alzheimer´s disease. We found previously unknown properties of axonal transport, including that cargo movement in vivo in both anterograde and retrograde directions follows multiple velocity modes.