Izraženost LRP1 receptora u hipokampalnoj formaciji zdravih i osoba oboljelih od Alzheimerove bolesti

master's thesis

• Title (english): Expression of LRP1 receptor in the hippocampal formation in healthy people and persons suffered from Alzheimer's disease
• Author: Emma Štampar
• Mentor: Lidija Šver (mentor)
• Committee member: Blaženka Kos (predsjednik povjerenstva)
• Committee member: Goran Šimić (član povjerenstva)
• Committee member: Reno Hrašćan (član povjerenstva)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Biology and Microbial Genetics); Zagreb
• Defense date and country: 2022-09-23, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Posljednjih godina sve više istraživanja upućuje na uključenost LRP1 proteina u patogenezu Alzheimerove bolesti (AD), najčešćeg primarnog uzroka sindroma demencije. LRP1 protein je član LDL obitelji receptora s višestrukim ulogama od kojih je potencijalno najvažnija posredovanje unosa kolesterola u stanice, napose neurone, a mnoge druge uloge povezane su s metabolizmom prekursornog proteina za amiloid (APP), dok su neke povezane sa signalnim putovima tau proteina. Stoga je svrha ovog istraživanja bila ispitati razine izraženosti LRP1 proteina u hipokampusu osoba oboljelih od AD-a te osoba umrlih zbog drugih uzroka koje nisu imale neuroloških ili psihijatrijskih smetnji, odnosno ustanoviti je li povećana ili smanjena ekspresija LRP1 proteina povezana s neuropatološkim promjenama karakterističnima za AD, napose neurofibrilarnom degeneracijom. Rezultati analize šest postmortalnih uzoraka tkiva hipokampusa (triju od osoba s AD-om i triju od osoba umrlih od uzroka koji nisu bili neurološke naravi) dobiveni istodobnim prikazom LRP1 proteina i tau proteina fosforiliranog na epitopu Ser202/Thr205AT8 pomoću AT8 protutijela pokazali su povećane razine LRP1 proteina kod osoba oboljelih od AD-a u odnosu na kontrolne uzorke. Veći stupanj neurofibrilarnih promjena procijenjen AT8-imunoreaktivnošću neurona negativno je korelirao sa stupnjem izraženosti LRP1 proteina. Taj preliminarni rezultat potvrđuje inicijalnu hipotezu uključenosti LRP1 proteina u nastanak AD-a, ali za čvršći zaključak bilo bi potrebno analizirati puno veći broj uzoraka u različitim stadijima bolesti.

Abstract (english)

In recent years, accumulated evidence suggests the involvement of the LRP1 protein in the pathogenesis of Alzheimer's disease (AD), the most common primary cause of dementia syndrome. The LRP1 protein is a member of the LDL receptor family with multiple roles, of which the potentially most important is the mediation of cholesterol entry into cells, especially neurons, and many other roles are related to the metabolism of the amyloid precursor protein (APP), whereas some relate to tau protein signaling pathways. Therefore, the purpose of this research was to examine the expression levels of LRP1 protein in the hippocampus of persons who suffered from AD and persons who died due to other causes and did not have neurological or psychiatric disorders, i.e. whether increased or decreased expression of LRP1 protein is associated with neuropathological changes characteristic of AD, especially with neurofibrillary degeneration. The results of the analysis of six postmortem tissue samples of the hippocampus (three from persons with AD and three from persons who died of non-neurological causes) were obtained by the simultaneous visualization of LRP1 protein and tau protein phosphorylated on the Ser202/Thr205 epitope using the AT8 antibody showed increased LRP1 protein levels in AD patients compared to control samples. The greater levels of neurofibrillary changes assessed by neuronal AT8-immunoreactivity negatively correlated with the LRP1 protein expression levels. This preliminary result confirms the initial hypothesis on the involvement of the LRP1 protein in the development of AD, but for a firmer conclusion, it would be necessary to analyze a much larger number of samples in different stages of the disease.

• Keywords: LRP1 protein; Alzheimerova bolest; hipokampalna formacija; tau protein; imunofluorescencija
• Keywords (english): LRP1 protein; Alzheimer's disease; hippocampal formation; tau protein; immunofluorescence
• Language: croatian
• URN:NBN: urn:nbn:hr:159:387351
• Study programme: Title: Bioprocess Engineering; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva (magistar/magistra inženjer/inženjerka bioprocesnog inženjerstva)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-04-24 13:38:13