Stein TD, Anders NJ, Decarli C, Chan SL, Mattson MP, Johnson JA. Neutralization of transthyretin reverses the neuroprotective effects of secreted amyloid precursor protein (APP) in APPSW mice resulting in tau phosphorylation and loss of hippocampal neurons: support for the amyloid hypothesis. J Neurosci. 2004 Sep 1;24(35):7707-17. PubMed.

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  1. This paper is not really in favor of the cascade hypothesis: The neuroprotective role of sAPP could be lost in AD, in parallel to the amyloid marker. Loss of function of APP is not a part of the amyloid cascade (gain of toxic function).

    Second, in the cascade hypothesis (Hardy and Selkoe, Science 2002), tau pathology was fully ignored and put at the very end of the cascade.

    View all comments by Andre Delacourte

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