| First Author | Nilsson P | Year | 2015 |
| Journal | Am J Pathol | Volume | 185 |
| Issue | 2 | Pages | 305-13 |
| PubMed ID | 25433221 | Mgi Jnum | J:218179 |
| Mgi Id | MGI:5616955 | Doi | 10.1016/j.ajpath.2014.10.011 |
| Citation | Nilsson P, et al. (2015) Autophagy-Related Protein 7 Deficiency in Amyloid beta (Abeta) Precursor Protein Transgenic Mice Decreases Abeta in the Multivesicular Bodies and Induces Abeta Accumulation in the Golgi. Am J Pathol 185(2):305-13 |
| abstractText | Alzheimer disease (AD) is biochemically characterized by increased levels of amyloid beta (Abeta) peptide, which aggregates into extracellular Abeta plaques in AD brains. Before plaque formation, Abeta 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 Abeta metabolism. In addition to a degradative role of autophagy in Abeta metabolism we recently showed that Abeta secretion is inhibited in mice lacking autophagy-related gene 7 (Atg7) in excitatory neurons in the mouse forebrain. This inhibition of Abeta secretion leads to intracellular accumulation of Abeta. Here, we used fluorescence and immunoelectron microscopy to elucidate the subcellular localization of the intracellular Abeta accumulation which accumulates in Abeta precursor protein mice lacking Atg7. Autophagy deficiency causes accumulation of p62(+) aggregates, but these aggregates do not contain Abeta. However, knockdown of Atg7 induced Abeta accumulation in the Golgi and a concomitant reduction of Abeta in the multivesicular bodies. This indicates that Atg7 influences the transport of Abeta possibly derived from Golgi to multivesicular bodies. |
