• Marianne Juul Madsen
Objective: Dementia is a growing problem, especially in the industrial world, because the life expectancy is increasing. At the moment 10-30 % of the world’s population above 65 years of age are effected of Alzheimer’s disease, with most cases being sporadic. Many studies of Alzheimer’s disease have been made, but to date no one have been able to fully explain the different pathological hallmarks, how different factor affect the disease, e.g. stress and sleep deprivation, or why the disease develops in some people. This project aims to investigate the proteomes in hippocampus of both mice with Alzheimer’s disease (APPPS1-21 mice) and wild-type mice with and without exposure to chronic stress.
Methods: To create an overview of the proteins in the different test subjects SDS-page was performed. Afterwards was filter-aided samples preparation (FASP) used to prepare the hippocampus samples for label free quantification using a Thermo-Electron QExactive HF-X mass spectrometer (ThermoFisher Scientific). PERSEUS (Max Planck Institute of biochemistry, v1.6.5.0) and PEAKS Studio X (Bioinformatics Solutions Inc.) were used in order to work with the data, make figures, and any statistical analyses, e.g. volcano plots, Hawaii plots, and Principal Component Analysis (PCA).
Results: The results of the SDS-page did not show any differences between the different mice or between test groups. Both volcano plots and the Hawaii plots showed a significant number proteins that have been either upregulated or downregulated in the different test groups, including proteins involved in the circadian cycle, as well as ApoE, APP, and GFAP, which all are suspected as being involved with Alzheimer’s disease. The PCA showed no clear groups of proteins involved in the way the results grouped except those involved in the circadian cycle.
Conclusion: The experiments resulted in several interesting results for the research in Alzheimer’s disease. ApoE, which has been implicated in the risk of developing familiar Alzheimer’s disease, was found significantly increased in APPPS1-21, whereas it was decreased in mice that have been exposed to stress, and in APPPS1-21 + CMS to an extend that it similar to the wild-type mice. Several proteins involved in the circadian cycle was also found to significantly altered in all test groups compared to the healthy wild-type mice, which can be related to the studies of the effect of sleep deprivation on the accumulation of -amyloid, also in healthy test subjects.
Publication date31 May 2019
Number of pages48
External collaboratorH. Lundbeck A/S
PhD fellow Amalie Clement amcl@lundbeck.com
ID: 304812347