Different Amyloid-β Self-Assemblies Have Distinct Effects on Intracellular Tau Aggregation
Authors: Lin Jiang
Jing Di
Woo Shik Shin
Gal Bitan
Kevin A Murray
Binsen Li
Chuanqi Sun
Journal: Frontiers in Molecular Neuroscience (2019)
Discipline: NEUROSCIENCE & BEHAVIOR
Keywords: Alzheimer’s disease; amyloid beta; biosensor cell; oligomer; tau.
Affiliations: Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, United States., Department of Chemistry and Biochemistry, UCLA-DOE Institute, University of California, Los Angeles, Los Angeles, CA, United States., Department of Biological Chemistry, UCLA-DOE Institute, University of California, Los Angeles, Los Angeles, CA, United States., Brain Research Institute, University of California, Los Angeles, Los Angeles, CA, United States., Molecular Biology Institute, University of California, Los Angeles, Los Angeles, CA, United States.

Abstract:  Alzheimer's disease (AD) pathology is characterized by the aggregation of beta-amyloid (Aβ) and tau in the form of amyloid plaques and neurofibrillary tangles in the brain. It has been found that a synergistic relationship between these two proteins may contribute to their roles in disease progression. However, how Aβ and tau interact has not been fully characterized. Here, we analyze how tau seeding or aggregation is influenced by different Aβ self-assemblies (fibrils and oligomers). Our cellular assays utilizing tau biosensor cells show that transduction of Aβ oligomers into the cells greatly enhances seeded tau aggregation in a concentration-dependent manner. In contrast, transduced Aβ fibrils slightly reduce tau seeding while untransduced Aβ fibrils promote it. We also observe that the transduction of α-synuclein fibrils, another amyloid protein, has no effect on tau seeding. The enhancement of tau seeding by Aβ oligomers was confirmed using tau fibril seeds derived from both recombinant tau and PS19 mouse brain extracts containing human tau. Our findings highlight the importance of considering the specific form and cellular location of Aβ self-assembly when studying the relationship between Aβ and tau in future AD therapeutic development. 

Retracted: Yes

PubPeer comments:
 This article contains several instances in which an image has been duplicated within or between figures. Figure 1C of this paper contains two panels (highlighted in red) that are the same image, although the two images are cropped differently. According to the labels, these panels should depict different experiments using biosensor cells exposed to different concentrations of Au03b2, and so one would not expect the images to be the same. The same image reappears in Figure 3B (highlighted in red). According to the figure label, this panel should be depicting cells that were not treated with Au03b2, so, again, one would not expect the image to be the same. In Figure 2B, a different image has been duplicated, though again the cropping is different (see the panels outlined in yellow). Again, these panels should depict different cells exposed to different experimental treatments (No Au03b2 treatment vs. Au03b2 oligomer treatment). Finally, Figure 2B and Figure 3B also share an image (see the panels outlined in blue) in a way one would not expect given the description of the experiments. Figure 1C: ![file] Figure 3B: ![file] Figure 2B: ![file] , 
 #1 Thank you for your attention to certain duplicated figures in our publication. As a corresponding author of this manuscript, I apologize for making this error, first of all. As indicated, I confirm that the two panels in Figure 1c are the same as the one in Figure 3B, and there are also duplicated images in Figure 2B. We seriously have taken steps to investigate the error. We managed to prepare correct figures and contact the editorial office for the correction. Our response to your comments are as follows. First, the conclusion of the manuscript is not based on the fluorescent images of intracellular tau aggregation, but the quantification using flow cytometry. The flow cytometry quantification is a method independent from the fluorescent images, and thus the error of the fluorescent images will not affect the conclusion of the manuscript. We reported both the fluorescent images and flow cytometry quantification in this manuscript. For example, Figures 1C, 2B and 3B show the single snapshot of fluorescent images of treated tau biosensor cells in representative experiment conditions. We also reported the flow cytometry quantification of the same treated cells in each experiment condition in the same figures (Figure 1D, 2B and 3B, respectively). And the data of flow cytometry quantification are from multiple replicates for each experimental condition (Figure 1D: nine replicates; Figure 2B: nine replicates; Figure 3B: six replicates for each experimental condition). As fluorescent cell image is qualitative evaluation, we rely on the flow cytometry quantification to draw all the conclusions. Therefore, the conclusion of the manuscript remains the same in spite of the errors in the fluorescent images. Second, we again apologize for making the error over the fluorescent cell images, even though it can not affect the conclusion of the manuscript. After we went through the notes, original data and images, we found that the error was introduced during the preparation and revision of manuscript figures. In manuscript preparation, we were handling a large amount of images (cells images from over 50 different experimental conditions). During the figure rearrangement in multiple manuscript revisions, we mistakenly duplicated several image panels, because those fluorescent cell images are very similar (that is also the reason why we chose the flow cytometry quantification to draw all the conclusions). We should have identified the figure duplication when we checked the manuscript before publication, but in regret we did not. We have prepared the correct figures and are contacting the editorial office for the correction. We are going to post the decision as soon as possible. Again, I feel sorry for causing this confusion and would like to give thanks for your attention to our publication. Best, Lin (in behalf of all coauthors) , 
 See additional concern with Figure 1c. Difficult to understand how this would occur solely due to the improper selection during figure assembly. *** ![file] , 
 Another issue in 2B (magenta boxes). I am not sure this was previously identified by the original poster or the authors. *** ![file] , 
 23 September 2021 The journal retracts the 08 November 2019 article cited above. Following publication, concerns were raised regarding the integrity of the images in the published figures. The authors failed to provide a satisfactory explanation during the investigation, which was conducted in accordance with Frontiers policies. This retraction was approved by the Chief Editors of Frontiers in Molecular Neuroscience and the Chief Executive Editor of Frontiers. The authors did not agree to this retraction. ,