title: Autophagy-related protein 7 deficiency in amyloid β (Aβ) precursor protein transgenic mice decreases Aβ in the multivesicular bodies and induces Aβ accumulation in the Golgi.
abstract: Alzheimer disease (AD) is biochemically characterized by increased levels of amyloid β (Aβ) peptide, which aggregates into extracellular Aβ plaques in AD brains. Before plaque formation, Aβ 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 Aβ metabolism. In addition to a degradative role of autophagy in Aβ metabolism we recently showed that Aβ secretion is inhibited in mice lacking autophagy-related gene 7 (Atg7) in excitatory neurons in the mouse forebrain. This inhibition of Aβ secretion leads to intracellular accumulation of Aβ. Here, we used fluorescence and immunoelectron microscopy to elucidate the subcellular localization of the intracellular Aβ accumulation which accumulates in Aβ precursor protein mice lacking Atg7. Autophagy deficiency causes accumulation of p62(+) aggregates, but these aggregates do not contain Aβ. However, knockdown of Atg7 induced Aβ accumulation in the Golgi and a concomitant reduction of Aβ in the multivesicular bodies. This indicates that Atg7 influences the transport of Aβ possibly derived from Golgi to multivesicular bodies.
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, Japan; Center for Alzheimer Research, Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Huddinge, Sweden. Electronic address: per-nilsson@brain.riken.jp.
authors.forename: Per
authors.initials: P
authors.lastname: Nilsson
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Misaki
authors.initials: M
authors.lastname: Sekiguchi
authors.affiliation: Support Unit for Animal Resources Development, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Akagi
authors.affiliation: Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Izumi
authors.affiliation: Department of Cell Biology, Unit of Basic Medical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Komori
authors.affiliation: Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Kelvin
authors.initials: K
authors.lastname: Hui
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Karin
authors.initials: K
authors.lastname: Sörgjerd
authors.affiliation: Laboratory for Protein Conformation Diseases, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Motomasa
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Biotechnology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Nobuhisa
authors.initials: N
authors.lastname: Iwata
authors.affiliation: Laboratory for Proteolytic Neuroscience, RIKEN Brain Science Institute, Wako, Saitama, Japan.
authors.forename: Takaomi C
authors.initials: TC
authors.lastname: Saido
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000071193:Autophagy-Related Protein 7; D006056:Golgi Apparatus / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000172:deficiency* / Q000378:metabolism; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism*; D066329:Protein Aggregates
chemical_list: D016229:Amyloid beta-Peptides; C502661:Atg7 protein, mouse; D008869:Microtubule-Associated Proteins; D010446:Peptide Fragments; D066329:Protein Aggregates; C078592:amyloid beta-protein (1-40); D000071193:Autophagy-Related Protein 7