Long-term exposition to a high fat diet favors the appearance of β-amyloid depositions in the brain of C57BL/6J mice. A potential model of sporadic Alzheimer’s disease
Authors: Mercè Pallàs
Miren Ettcheto
Ester Verdaguer
Carme Auladell
Antoni Camins
Carlos Beas-Zarate
Oriol Busquets
Jaume Folch
Journal: Mechanisms of Ageing and Development (2017)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: AD; AMP-activated protein kinase; AMPK; ANS; Alzheimer’s disease

Abstract:  Aims: The sporadic and late-onset form of Alzheimer's disease (AD) constitutes the most common form of dementia. This non-familiar form could be a consequence of metabolic syndrome, characterized by obesity and the development of a brain-specific insulin resistance known as type III diabetes. This work demonstrates the development of a significant AD-like neuropathology due to these metabolic alterations. Methods: C57BL/6J mice strain were divided into two groups, one fed with a diet rich in palmitic acid (high-fat diet, HFD) since their weaning until 16 months of age, and another group used as a control with a regular diet. The analyses were carried out in the dentate gyrus area of the hippocampus using a Thioflavin-S stain and immunofluorescence assays. Results: The most significant finding of the present research was that HFD induced the deposition of the βA peptide. Moreover, the diet also caused alterations in different cell processes, such as increased inflammatory reactions that lead to a decrease in the neuronal precursor cells. In addition, the results show that there were also dysregulations in normal autophagy and apoptosis, mechanisms related to βA formation. Conclusions: The present findings confirm that HFD favors the formation of βA depositions in the brain, a key feature of AD, supporting the metabolic hypothesis of sporadic AD. 

Retracted: No

PubPeer comments:
 Welp. Several images in this paper have many repeated internal features, a sample shows below. I would be interested to hear an explanation from the authors. TAM. *** ![file] , 
 Dear Prof. Actinopolyspora Biskrensis Thank you very much for your interest in our work. The image has not been modified or any type of manipulation has been carried out. They are images taken under the microscope after labeling with the corresponding fluorescently labeled primary and secondary antibodies. Therefore, I repeat that it is IMPOSSIBLE to paint, draw etc on these images. , 
 #2  Therefore, I repeat that it is IMPOSSIBLE to paint, draw etc on these images. No-one has asserted that the images were painted, drawn or Photoshopped. But the question remains, what immunohistochemical phenomena create repeated sections within an image? The red fluorescence, I gather from the figure legends, identifies astrocytes (or the GFAP within astrocytes) while the blue is a Hoechst dye (33258 or 33342, I imagine) and identifies bands of DNA. What is the phenomenon that induced so many astrocytes into identical postures? Surely it deserves closer study. , 
 #3 Thank you for your suggestions , 
 Here is a look at Figure 3. *** ![file] , 
 Figure 6. *** Enhanced brightness ![file] , 
 #1 I might have found more repeated internal features in Figure 2, left panel CT: ![file] , 
 #5 Another look at Fig 3 with the blue channel turned down (to reduce the Hoechst stain): ![file] , 
 #2 Dr. Camins - The suggestion that it is  IMPOSSIBLE to paint, draw etc on these images is easily disproven. Any photograph can be painted or drawn upon, as I would think most people are aware. As an illustration of how easy it would be to artificially add additional astrocytes to a photo, I have added over 20 more of this particular feature ![file] to the original image to create the photo below. Although I am not proficient with Photoshop, this manipulated image seems to demonstrate that it is not IMPOSSIBLE to construct an image in this way. ![file] , 
 The authors regret that there are some (sic) errors in the original Figures 2, 3 and 5. A reader brought to our attention that there was a manipulation in the figures of the GFAP and IBA1 inmunohistochemistry in the control group and mice treated with a high fat diet in the hippocampus. After consulting with experts, the authors confirm, that these accidental duplications in the photographs of cell antibodies are due to problems with the camera.* Hence, the authors declare that the errors in the photographs are not intentional. Indeed, the results of the study have been maintained at all times, showing that high fat diet causes an activation of the glial cells that is associated with neuroinflammation in the hippocampus. Therefore, the results of our study are experimentally reproducible, as we and other laboratories have reported in later publications and do not alter the conclusions of the manuscript at any time. The corrected version of Figures 2, 3 and 5 has been provided and replaced. The authors would like to apologise for any inconvenience caused. ![file] ![file] ![file] ***  * It would be appreciated if the authors could make these  experts available for interview. It should be alarming to other users of the same equipment (Olympus BX61, I believe) that mistaken results such as yours could be generated by professional (and expensive) laboratory equipment. I would go so far as to suggest you contact the manufacturer to request a refund. Can you explain if this is a problem that has affected other results of your lab? Should other papers be examined? , 
 I completely agree with Actinopolyspora biskrensis. The repetitive elements are very hard to explain by microscopy errors, but very easy to explain by e.g. copy pasting elements manually, e.g. by photoshopping. I am appalled by the Editor s decision to address such apparent manipulation of photos with a Correction ([here] ). , 
 You might correct an error but you cannot correct a falsification which is also the official [COPE] opinion. Editors should consider retracting a publication if: They have clear evidence that the findings are unreliable, either as a result of major error (eg, miscalculation or experimental error), or as a result of fabrication (eg, of data) or falsification (eg, image manipulation). ,