Autophagy-Related Protein 7 Deficiency in Amyloid beta (A beta) Precursor Protein Transgenic Mice Decreases A beta in the Multivesicular Bodies and Induces A beta Accumulation in the Golgi

作者：Nilsson Per^*; Sekiguchi Misaki; Akagi Takumi; Izumi Shinichi; Komor Toshihisa; Hui Kelvin; Soergjerd Karin; Tanaka Motomasa; Saito Takashi; Iwata Nobuhisa; Saido Takaomi C

来源：American Journal Of Pathology, 2015, 185(2): 305-313.

DOI：10.1016/j.ajpath.2014.10.011

Alzheimer disease (AD) is biochemically characterized by increased levels of amyloid beta (A beta) peptide, which aggregates into extracellular A beta plagues in AD brains. Before plague formation, A beta accumulates intracellularly in both AD brains and in the brains of AD model mice, which may contribute to disease progression. Autophagy, which is impaired in AD, clears cellular protein aggregates and participates in A beta metabolism. In addition to a degradative role of autophagy in All metabolism we recently showed that A beta secretion is inhibited in mice Lacking autophagy-related gene 7 (Atg7) in excitatory neurons in the mouse forebrain. This inhibition of A beta secretion Leads to intracellular accumulation of A beta. Here, we used fluorescence and immunoelectron microscopy to elucidate the subcellular Localization of the intracellular A beta accumulation which accumulates in All precursor protein mice lacking Atg7. Autophagy deficiency causes accumulation of p62(+) aggregates, but these aggregates do not contain A beta. However, knockdown of Atg7 induced A13 accumulation in the Golgi and a concomitant reduction of A beta in the multivesicular bodies. This indicates that Atg7 influences the transport of All possibly derived from Golgi to multivesicular bodies.

• 出版日期2015-2