Maia LF, Kaeser SA, Reichwald J, Lambert M, Obermüller U, Schelle J, Odenthal J, Martus P, Staufenbiel M, Jucker M. Increased CSF Aβ during the very early phase of cerebral Aβ deposition in mouse models. EMBO Mol Med. 2015 May 15;7(7):895-903. PubMed.

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  1. Previously, we found that Aβ secretion from neurons is mediated by autophagy. In addition, it has been shown previously that autophagosomes contain both Aβ and the Aβ-generating enzymes (Nilsson et al., 2013; Nilsson et al., 2015). The increased levels of Aβ in CSF from younger APP Tg mice which the authors have found in this study could, at least partially, possibly be due to increased autophagy in the early stage of the APP mice—that is, if we assume CSF to be an indicator of brain ISF.

    Data from humans has indeed shown an upregulation of autophagy in early AD, for example as a response to an imbalance in proteostasis or oxidative stress. Therefore it would be interesting to know if the initial increase in Aβ secretion is paralleled by an increase of autophagy, which could be investigated biochemically in the APP Tg mice (Nilsson and Saido, 2014).

    References:

    Nilsson P, Loganathan K, Sekiguchi M, Matsuba Y, Hui K, Tsubuki S, Tanaka M, Iwata N, Saito T, Saido TC. Aβ secretion and plaque formation depend on autophagy. Cell Rep. 2013 Oct 17;5(1):61-9. PubMed.

    Nilsson P, Sekiguchi M, Akagi T, Izumi S, Komori T, Hui K, Sörgjerd K, Tanaka M, Saito T, Iwata N, Saido TC. 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. Am J Pathol. 2015 Feb;185(2):305-13. Epub 2014 Nov 26 PubMed.

    Nilsson P, Saido TC. Dual roles for autophagy: degradation and secretion of Alzheimer's disease Aβ peptide. Bioessays. 2014 Jun;36(6):570-8. Epub 2014 Apr 8 PubMed.

    View all comments by Takaomi Saido

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