Journal of Alzheimers Disease & Parkinsonism
Open Access

Abstract

The �?²-amyloid precursor protein (APP) has been extensively studied for its role as the precursor of the �?²-amyloid protein (A�?²) in Alzheimerâ�?�?s disease (AD). However, our understanding of the normal function of APP is still patchy. Emerging evidence indicates that a dysfunction in APP trafficking and degradation can be responsible for neuronal deficits and progressive degeneration in humans. We recently reported that Y682 mutation on the 682-YENPTY-687 domain of APP, devoted to APP internalization and trafficking (1) affects APP binding to some specific adaptors leading to an anomalous compartmentalization of APP, defects in the autophagy machinery, progressive premature neuronal degeneration and dementia in mice (2-3). A comparative Mass spectrometry analysis between mutated and control mice leaded to the identification of some crucial proteins that might be probably responsible of the phenotype observed in mutated mice (2,3). Two of these proteins, named Clathrin and its adaptor, AP2, are part of a big protein complex controlling APP trafficking inside neurons (4). Notably, the relevance of these proteins in the APP pathway and functions was further demonstrated in neuronal progenitors from Alzheimerâ�?�?s disease patients. Overall, our results consolidate and refine the importance of APP adaptors in APP normal functions from an animal model of premature aging/dementia and from human differentiated stem cells. Additionally, they open the perspective to consider these adaptors as potential targets for the design and development of new therapeutic strategies.

Biography

Email: matrone@biomed.au.dk