The role of neuronal intracellular traffic in Alzh.. (TRAFFICINAD)
The role of neuronal intracellular traffic in Alzheimer´s disease
Start date: Apr 1, 2013,
End date: Mar 31, 2017
In neurons of Alzheimer’s disease (AD) there is an aberrant accumulation of beta-amyloid (Aβ) at synapses that renders difficult the formation of new memories for AD patients. Intracellular trafficking abnormalities have been implicated in Aβ accumulation. This research project aims to define how neuronal intracellular trafficking is mechanistically involved in Aβ accumulation that leads to AD. We will determine how the intracellular itinerary of the amyloid precursor protein in neurons influences the generation of Aβ. We will determine the intracellular trafficking of lysosomal hydrolases in neurons and their contribution to the lysosomal clearance of Aβ. Furthermore, we will investigate the mechanism whereby regulators of intracellular trafficking identified as risk-factors for AD contribute to Aβ accumulation. Finally, because aging is the most important risk factor for AD, we will determine if alterations in intracellular trafficking occur in aging, identifying a new mechanism of vulnerability to neurodegeneration in AD. Thus, we will demonstrate how intracellular trafficking is implicated in AD and unravel an important disease mechanism.
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