Sherman MA, LaCroix M, Amar F, Larson ME, Forster C, Aguzzi A, Bennett DA, Ramsden M, Lesné SE. Soluble Conformers of Aβ and Tau Alter Selective Proteins Governing Axonal Transport. J Neurosci. 2016 Sep 14;36(37):9647-58. PubMed.
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Mary S. Easton Center for Alzheimer's Disease Research at UCLA
This is an important advance that builds on our understanding of key contributors to Aβ-induced deficits in axonal transport. Sherman et al. have created unique models in which to assess for Aβ and tau pathological interactions. They demonstrated that axonal transport deficits in AD models involve Aβ trimers, the increased levels of Alz50+ tau conformers, and that the effects of these tau species is to lower KLC-1 levels. This cascade occurs within 60 minutes in vitro. As the authors point out, there are many potential mechanisms by which Aβ trimers could induce tau-dependent loss of KLC-1. The brief time window in which Aβ/tau interactions occur, as observed in this paper as well as previous studies, including ours (Vossel et al., 2010 and 2015; Zempel et al., 2013) provides a unique opportunity to dissect mechanisms involved. It will be exciting to see how this model develops and whether new effective therapies can emerge based on such insights into Aβ/tau interactions.
References:
Vossel KA, Zhang K, Brodbeck J, Daub AC, Sharma P, Finkbeiner S, Cui B, Mucke L. Tau reduction prevents Abeta-induced defects in axonal transport. Science. 2010 Oct 8;330(6001):198. PubMed.
Vossel KA, Xu JC, Fomenko V, Miyamoto T, Suberbielle E, Knox JA, Ho K, Kim DH, Yu GQ, Mucke L. Tau reduction prevents Aβ-induced axonal transport deficits by blocking activation of GSK3β. J Cell Biol. 2015 May 11;209(3):419-33. PubMed.
Zempel H, Luedtke J, Kumar Y, Biernat J, Dawson H, Mandelkow E, Mandelkow EM. Amyloid-β oligomers induce synaptic damage via Tau-dependent microtubule severing by TTLL6 and spastin. EMBO J. 2013 Nov 13;32(22):2920-37. PubMed.
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