Proteome analysis of APPPS1-21 and wild-type mice - A novel chronic stress model
Author
Madsen, Marianne Juul
Term
4. term
Publication year
2019
Submitted on
2019-05-31
Pages
48
Abstract
Alzheimers sygdom er en stigende udfordring i takt med, at vi lever længere, og det anslås, at 10–30 % af personer over 65 år er ramt. Forskere kan endnu ikke fuldt ud forklare, hvorfor sygdommen opstår, hvordan de karakteristiske forandringer i hjernen udvikler sig, eller hvordan faktorer som stress og søvnmangel påvirker den. I dette studie undersøgte vi proteomet – det samlede sæt af proteiner – i hippocampus, et hjerneområde vigtigt for hukommelse, hos mus der udvikler Alzheimer‑lignende forandringer (APPPS1‑21‑mus) og hos raske (wild‑type) mus, med og uden langvarig stress. Metoder: Proteinblandingerne blev først adskilt for at give et overblik og derefter analyseret detaljeret med højopløselig massespektrometri, som kan identificere og kvantificere tusindvis af proteiner uden mærkning. Dataene blev undersøgt med statistiske værktøjer, der fremhæver proteiner, som øges eller mindskes mellem grupper, herunder en mønstergenkendelses‑analyse (principal component analysis, PCA). Resultater: Den indledende adskillelse viste ikke tydelige forskelle mellem grupperne. Den dybere analyse viste derimod, at mange proteiner var signifikant op‑ eller nedreguleret på tværs af grupper. Det gjaldt blandt andet proteiner knyttet til døgnrytmen (den circadiane cyklus) og kendte Alzheimer‑relaterede proteiner som apolipoprotein E (ApoE), amyloid‑prækursor‑protein (APP) og glialt fibrillært surt protein (GFAP). PCA adskilte ikke grupperne klart, bortset fra mønstre relateret til døgnrytme‑proteiner. Konklusion: ApoE, et protein forbundet med risikoen for Alzheimers, var signifikant forhøjet i APPPS1‑21‑mus, nedsat i stressede mus, og hos APPPS1‑21‑mus udsat for stress var niveauet reduceret mod de værdier, der sås hos raske mus. Proteiner involveret i døgnrytmen var markant ændrede i alle testgrupper sammenlignet med raske mus, i tråd med studier der kobler søvndeprivation til ophobning af β‑amyloid – også hos raske forsøgspersoner.
Alzheimer’s disease is a growing challenge as people live longer, with estimates that 10–30% of those over 65 are affected. Researchers still cannot fully explain why it develops, how hallmark brain changes arise, or how factors such as stress and sleep loss influence it. This study examined the set of proteins (the proteome) in the hippocampus, a brain region important for memory, in mice that develop Alzheimer‑like changes (APPPS1‑21 mice) and in healthy wild‑type mice, with and without long‑term stress. Methods: Protein mixtures were first separated to provide an overview, then analyzed in detail with high‑resolution mass spectrometry, which identifies and quantifies thousands of proteins without labels. The data were explored with statistical tools that highlight proteins that increase or decrease between groups, including a pattern analysis (principal component analysis, PCA). Results: The initial separation did not reveal obvious differences between the groups. However, deeper analysis showed that many proteins were significantly up‑ or down‑regulated across groups. These included proteins linked to daily biological rhythms (the circadian cycle) and well‑known Alzheimer‑related proteins such as apolipoprotein E (ApoE), amyloid precursor protein (APP), and glial fibrillary acidic protein (GFAP). PCA did not separate the groups clearly, except for patterns related to circadian proteins. Conclusion: ApoE, a protein associated with Alzheimer’s risk, was significantly increased in APPPS1‑21 mice, decreased in stressed mice, and in APPPS1‑21 mice exposed to stress it was reduced toward the levels seen in healthy wild‑type mice. Proteins involved in circadian rhythms were significantly altered in all test groups compared with healthy mice, aligning with studies linking sleep deprivation to the accumulation of β‑amyloid, including in healthy subjects.
[This abstract was generated with the help of AI]
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