Zhang H, Zhu X, Pascual G, Wadia JS, Keogh E, Hoozemans JJ, Siregar B, Inganäs H, Stoop EJ, Goudsmit J, Apetri A, Koudstaal W, Wilson IA. Structural Basis for Recognition of a Unique Epitope by a Human Anti-tau Antibody. Structure. 2018 Dec 4;26(12):1626-1634.e4. Epub 2018 Oct 11 PubMed.

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Comments

  1. This article describing the structure and binding properties of the CBTAU-24.1 antibody is a nice addition to similar reports in recent years of various tau antibodies against different epitopes. It would be informative to know if this antibody is the same one that Janssen has in clinical trials targeting the mid-region of tau as a potential therapy for Alzheimer’s disease. If not, how do they differ? It would also be interesting to find out how the Janssen antibody(ies) against this region differ from the UCB tau antibody in clinical trials. That one has been reported to recognize tau 235–246, which is similar to the epitope of the one reported here.

    The affinity of the CBTAU-24.1 antibody appears to be rather low (0.3-2.5 µM) but our studies indicate that higher affinity does not necessarily translate into better efficacy (Congdon et al., 2016). A word of caution is that it is not accurate to describe this antibody as recognizing the entire population of (aggregated) tau subspecies as mentioned in the last paragraph of the article. As reported, its binding to tau is partially phospho-dependent, with about eightfold higher affinity for its phospho- versus non-phospho-epitope but interestingly is blocked by phospho-serine 237. Therefore, like all tau antibodies, it will only recognize a certain pool of tau proteins, which is the best we can do.

    Xiangpeng Kong is a co-author of this comment. 

    References:

    Congdon EE, Lin Y, Rajamohamedsait HB, Shamir DB, Krishnaswamy S, Rajamohamedsait WJ, Rasool S, Gonzalez V, Levenga J, Gu J, Hoeffer C, Sigurdsson EM. Affinity of Tau antibodies for solubilized pathological Tau species but not their immunogen or insoluble Tau aggregates predicts in vivo and ex vivo efficacy. Mol Neurodegener. 2016 Aug 30;11(1):62. PubMed.

    View all comments by Einar Sigurdsson

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  1. New Antibody Binds to Mid-Region, and Aggregates, of Tau