In addition, Aβ oligomers seeds tau oligomerization ( Lasagna-Reeves et al., 2010). Consequently, it seems likely that Aβ oligomers, but not the fibrillar form of Aβ, induced tau hyperphosphorylation ( De Felice et al., 2008) and neuritic degeneration ( Jin et al., 2011) in cells overexpressing human tau and in mice overexpressing human wild-type (WT) tau ( Chabrier et al., 2012). Growing evidence implicates small soluble oligomeric assembles of misfolded amyloids as critical pathogenic species ( Haass and Selkoe, 2007 Lasagna-Reeves et al., 2011a Castillo-Carranza et al., 2013a, b). Furthermore, it is well established that aggregated Aβ is an important contributor to tau phosphorylation, mislocalization, and aggregation in animal models and cell cultures ( Busciglio et al., 1995 Götz et al., 2001 Ferrari et al., 2003 De Felice et al., 2008 Ittner et al., 2010).
Although amyloid pathology lies upstream of, or parallel to, tau pathology ( Oddo et al., 2003 Small and Duff, 2008), current evidence suggests that tau is a direct casual mediator of amyloid β protein (Aβ) toxicity ( Rapoport et al., 2002 Roberson et al., 2007 Nussbaum et al., 2012 Bloom, 2014). In Alzheimer's disease (AD), amyloid plaques and neurofibrillary tangles (NFTs) are considered responsible for disease progression ( Selkoe, 2001).
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