Elliott C, Rojo AI, Ribe E, Broadstock M, Xia W, Morin P, Semenov M, Baillie G, Cuadrado A, Al-Shawi R, Ballard CG, Simons P, Killick R. A role for APP in Wnt signalling links synapse loss with β-amyloid production. Transl Psychiatry. 2018 Sep 20;8(1):179. PubMed.

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  1. The observation by Elliot et al. that the Wnt-PCP pathway affects the processing of APP is original and interesting. However, we already published in 2015 that DKK1 increases the generation of amyloid-β by affecting the transcription of BACE1 (Parr et al., 2015). In fact, we reported that β-catenin binds specifically to regions within the promoter of BACE1 containing putative T-cell factor/lymphoid enhancer binding factor-1 (TCF/LEF) motifs, consistent with canonical Wnt target regulation. Therefore, we proposed a different mechanism of action that does not involve the regulation of the non-amyloidogenic processing of APP.

    References:

    Parr C, Mirzaei N, Christian M, Sastre M. Activation of the Wnt/β-catenin pathway represses the transcription of the β-amyloid precursor protein cleaving enzyme (BACE1) via binding of T-cell factor-4 to BACE1 promoter. FASEB J. 2015 Feb;29(2):623-35. Epub 2014 Nov 10 PubMed.

    View all comments by Magdalena Sastre

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  1. Does APP Promote Synapse Loss, Aβ Production Through Wnt Signaling?