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

Per Nilsson, Misaki Sekiguchi, Takumi Akagi, Shinichi Izumi, Toshihisa Komori, Kelvin Hui, Karin Sörgjerd, Motomasa Tanaka, Takashi Saito, Nobuhisa Iwata, Takaomi C. Saido

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)305-313
Number of pages9
JournalAmerican Journal of Pathology
Volume185
Issue number2
DOIs
StatePublished - 2015
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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