Department of Bioinformatics and Functional Genomics, Institute of Pharmacy and Molecular Biotechnology, Heidelberg University, Im Neuenheimer Feld 364, 69120 Heidelberg, Germany.
Exp Brain Res. 2012 Apr;217(3-4):423-34. doi: 10.1007/s00221-011-2861-2. Epub 2011 Sep 20.
The amyloid precursor protein (APP) plays a key role in the pathogenesis of Alzheimer's disease (AD), as proteolytical cleavage of APP gives rise to the β-amyloid peptide which is deposited in the brains of Alzheimer patients. During the past years, intense research efforts have been directed at elucidating the physiological function(s) of APP and the question of whether a perturbation of these functions contributes to AD pathogenesis. Indeed, a growing body of evidence has accumulated supporting a role of APP and the two closely related homologues APLP1 and APLP2 in various aspects of nervous system development and function, in particular, for synapse formation and function. This review summarizes recent insights into the in vivo role of the APP gene family from mice lacking individual or combinations of APP family members, with particular emphasis on recently generated knockin mice to examine the in vivo relevance of distinct functional domains.
淀粉样前体蛋白（APP）在阿尔茨海默病（AD）的发病机制中起着关键作用，因为 APP 的蛋白水解切割产生β-淀粉样肽，该肽沉积在阿尔茨海默病患者的大脑中。在过去的几年中，人们进行了大量的研究，旨在阐明 APP 的生理功能以及这些功能的紊乱是否有助于 AD 的发病机制。事实上，越来越多的证据表明，APP 及其两个密切相关的同源物 APLP1 和 APLP2 在神经系统发育和功能的各个方面都发挥着作用，特别是在突触形成和功能方面。这篇综述总结了近年来从小鼠中缺失单个或多个 APP 家族成员，以及特别强调最近生成的基因敲入小鼠来研究不同功能域的体内相关性方面，对 APP 基因家族在体内作用的最新认识。
