Defective axonal transport in Alzheimer's disease

Alzheimer's dementia is caused by accumulation of amyloid-β protein in neurons, formed from proteolytisis of amyloid precursor protein (APP), but the normal role of APP in the brain remains unclear. In December 6, Nature Adeela Kamal and colleagues from University of California, San Diego show that APP is involved in transport within nerve cells and shunts cellular materials along the axons.

Kamal et al. investigated the role of APP in axonal transport by comparing the steady-state levels of kinesin-I (a microtubule motor protein) and putative kinesin-I cargoes in sciatic nerve axons, the dorsal root ganglion and corpus callosum from APP-null mutant and wild-type mice. They found that APP serves as a kinesin-I membrane receptor, mediating the axonal transport of β-secretase and presenilin-1 (Nature 2001, 414:643-648).

A previous study, from the same laboratory, demonstrated that proteolytic processing of APP generates a carboxy-terminal fragment of APP, which carries a cell death signal ...