Wang L, Benzinger TL, Su Y, Christensen J, Friedrichsen K, Aldea P, McConathy J, Cairns NJ, Fagan AM, Morris JC, Ances BM. Evaluation of Tau Imaging in Staging Alzheimer Disease and Revealing Interactions Between β-Amyloid and Tauopathy. JAMA Neurol. 2016 Sep 1;73(9):1070-7. PubMed.

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  1. The authors report that tau imaging with F-18 AV1451 can accurately distinguish healthy controls from AD. While important as part of validation of a new technique, this in itself is not very useful when an interview can do the job just as well in these straightforward, clinically defined cases. More important is the suggestion by the authors that amyloid may modify hippocampal tau to a more toxic form and that this then drives neurodegeneration of that structure. While an intriguing suggestion, the data is not very convincing due to small sample size. The suggestion relies on the finding that there is no significant difference in hippocampal tau in those with amyloid compared to those without, but that hippocampal volume loss is much greater when amyloid is present. But looking at the data points in figure 3, there is an indication that there is more tau in those with amyloid, suggesting the study may be underpowered and failed to detect this. So, it may be that amyloid is associated with more hippocampal tau and that the neurodegeneration is tau dose-related rather than due to conversion of tau to a more toxic form by amyloid. A larger study is needed to clarify this potentially very important issue.

    View all comments by Christopher Rowe

  2. A speculative, but intriguing, implication of these findings is that Aβ can facilitate the membrane channel forming properties of tau. Our recent paper on tau showed that it was capable of forming non-selective and potentially destructive ion channels in lipid membranes, but it was less active as a channel-former than Aβ. It is possible that Aβ may interact with tau to catalyze its entry into membranes, leading to cellular energy depletion, dysfunction, and eventually cell death. While we have some hints that this interaction takes place in vitro, demonstrating it in vivo could be very informative and perhaps lead to agents that block this deadly amyloid interaction.

    References:

    Patel N, Ramachandran S, Azimov R, Kagan BL, Lal R. Ion Channel Formation by Tau Protein: Implications for Alzheimer's Disease and Tauopathies. Biochemistry. 2015 Dec 22;54(50):7320-5. Epub 2015 Dec 7 PubMed.

    View all comments by Bruce Kagan

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  1. Brain Imaging Suggests Aβ Unleashes the Deadly Side of Tau