. Presenilin-1 Targeted Morpholino Induces Cognitive Deficits, Increased Brain Aβ1-42 and Decreased Synaptic Marker PSD-95 in Zebrafish Larvae. Neurochem Res. 2017 Oct;42(10):2959-2967. Epub 2017 Jun 16 PubMed.


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  1. Reading the title of this paper might mislead people to think that there is evidence that zebrafish produce a peptide similar to Aβ. However, while there are two “co-orthologues” of the APP gene in zebrafish (appa and appb), Aβ peptides cleaved from the protein products of these genes have not yet been detected. In fact, an analysis of the zebrafish Appa and Appb protein sequences did not find conservation of the human APP β-cleavage site (Moore et al., 2014). It appears that this site may have evolved only after the divergence of the teleost (bony fish) and tetrapod lineages. This implies that the zebrafish Appa and Appb proteins may not produce forms of Aβ although this is something that must be tested experimentally. We and collaborators are currently attempting to do this although it can be a challenge to prove a negative. If you examine Figure 6 in this paper you will see that western immunoblotting detected an “Aβ” signal at 87 kDa which, of course, has nothing to do with the expected size of an Aβ peptide. (Also, if you look at the particular human APP sequence against which the antibody they use is directed, this is not well conserved in either Appa or Appb proteins so it is not certain that the antibody is actually detecting these proteins). Of course, the paper makes no attempt to distinguish between Aβ1-42 and any other form of Aβ peptide, despite specifically naming Aβ1-42 in the paper title.

    If zebrafish do lack production of an amyloid-beta peptide this may make them an important system for examining the effects of fAD-like mutations without any possibility that such effects are mediated by Aβ.


    . Asynchronous evolutionary origins of Aβ and BACE1. Mol Biol Evol. 2014 Mar;31(3):696-702. Epub 2013 Dec 19 PubMed.

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