Alzheimer's disease in the brain develops several pathological metabolic processes involving different mediator systems. The multifaceted pathological process is the basis of the "abnormal" development of models of Alzheimer's disease. There are individual features of the development of this disease in humans.

There are two articles in the appendix that support this view.

Without more information it is difficult to comment.  Can you clarify a few things about your study?

-what type of fatty diet did you feed the mice- the same type of fat as Billings et al. 2005? at what age were the mice put on a fatty diet- the same age ast Billings et al., 2005? Were both Tg and control mice fed the fatty diet?

- were cognitive deficits seen in both groups of Tg mice (those fed a fatty diet and those on a standard diet?)  Did control mice show cognitive deficits on fatty diet?  on a standard diet? 

-did you look for regular tau or phosphorylated tau? (if pTau- which phosphorylation site?) Did you use western blot? immunohistochemistry? Which brain areas?

-Which type of amyloid did you look for? Did you use western blot? immunohistochemistry? Which brain areas? Did you look for APP?

This is probably not the format to ask and answer all these questions.  You could consider making this a Research Gate project and allow others to comment on it.  Might be especially helpful if you are in the early stages of your experiment. 

Good luck!  :)

 Thank You, Professor Kulchitsky for the attached files and your comments. 

Professor Bjugstad, Thank you for your suggestion and making me aware of my immaturity on expressing question in Research Gate. Professor, actually we had provided 60% high-fat diet and 10% normal diet to both 3xTg and non-Tg mice aged 8-week for 16-week duration. Memory impairment was assessed by morris water maze test and Y-maze in high-fat diet fed 3xTg AD mice (24-week age) only. Nonetheless, no any change in beta-amyloid oligomer and phospho-tau-T was observed irrespective of diet and genotype. On further analysis, we observed significant elevations in oxidative stress biomarker in 3xTg AD mice fed with high-fat diet as suggested by raised 4-HNE. Oxidative defense system was impaired and antioxidants were reduced as shown by reduction in p-NrF2,p-AKT, HO-1 and MnSod in transgenic mice fed with high-fat diet. Apoptosis was observed in the Trangenic mice fed with high-fat diet as Bax/BCL was significantly increased and caspase-3 was activated. All data were obtained from western blot analysis of cortex sample. 

Now I am wondering should I assume the all molecular finding I have obtained unravel memory impairment mechanism in a pre-ageing state of 3xTg AD mice or ageing state. It is postulated that 3xTg mice develop amyloid in 6 months, and p-tau after 10/12 month.  A study similar to mine (https://www.ncbi.nlm.nih.gov/pubmed/24630364) suggests that high-fat diet markedly aggravates memory impairment with no change in amyloid and tau pathology. I am getting a bit confusion to correlate my finding with respect to the age-matched condition of memory impairment and aid novelty in my work.  

Definitely, I will raise such queries in Research gate project in next time. Thank you professor :)  

Saroj,

It sounds like your study is very similar to the one you indicated.  I think the fact that you found changes in the redox system (oxidative stress and reduced antioxidants) is quite interesting. 

The problem with using transgenic mice is that you don't know how inbred (or outbred) your strain is compared to the published studies- affecting neuropathology and behavior- so don't be too discouraged.  Behavior testing can also vary from lab to lab- so it too is hard to compare. (PS. you should always behavior test your control animal groups.  If you only test the high-fat diet Tg group you really don't know if you have cognitive impairment or not without also testing the other 3 groups.) 

I think you have some good data there and you should pursue a publication.  Does the redox data correlate with behavior results or neuropathology (a-beta or ptau)?  Can you run westerns on other brain areas?  ie.  hippocampus?  I believe that the neuropathology in Alzheimers follows a certain progressive pattern- ie. septal and  hippocampal formations prior to cortical areas. 

Without strong data showing a-beta or ptau or cognitive loss, your data would suggest a early stage of disease (or pre-aging if you will).  The changes in the redox system could precede the emergence of plaques and tangles.  Do  those animals with the highest oxidative stress (or lowest antioxidant levels) also have the highest levels of a-beta (or ptau).  You may not have significant group effects but you could look for patterns on an individual levels. 

Good luck.  Cheers, Kim

Thank you Professor Bjugstad. Your suggestions are of utmost importance for me. I really appreciate for providing me with your valuable time, and ideas. I had conducted all my works in both wild-type non-Tg and 3xTg AD mice. Lipid peroxidation biomarker, 4HNE was significantly elevated in only 3xTg mice fed with HFD. We could not get any significant molecular findings/biomarkers with non-Tg mice’s cortex irrespective of food type, except a little bit memory impairment was observed in response to HFD as assessed by behavior test (Morris Water Maze and Y-Maze test).

As this research was a part of my MS thesis and because of time constraint, I could not more perform experiments with hippocampus sample. Nowadays, I am writing manuscript comprising all my findings and is supposed to submit for publication very soon. Your views have greatly supported me to give an intriguing outcome for my research work.  Once again, Thank you professor, for a very nice interaction I have had with you.