Analysis of tau protein spread in rat brain as a model of Alzheimer's disease

master's thesis

• Title (croatian): Analiza širenja proteina tau u mozgu štakora kao modela Alzheimerove bolesti
• Author: Emina Horvat Velić
• Mentor: Goran Šimić (mentor)
• Mentor: Dubravka Hranilović (sumentor)
• Committee member: Dubravka Hranilović (predsjednik povjerenstva)
• Committee member: Jasna Lajtner (član povjerenstva)
• Committee member: Martina Šeruga Musić (član povjerenstva)
• Committee member: Sofia Ana Blažević (član povjerenstva)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2021-11-17, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease and the most common primary cause of dementia syndrome. Many theories exist regarding possible mechanisms of development and progression of AD, one of which is the tau hypothesis. This theory suggests that the hyperphosphorylated tau proteins misfold, oligomerize and aggregate, disrupting microtubule structure and function ultimately leading to the death of synapses and neurons. In this work we investigated changes and spreading of tau fibrils and tau oligomers that were inoculated into the medial entorhinal cortex of nine Wistar rats. The phosphorylated tau proteins were visualised by using the AT8 antibody, which binds to Ser202/Thr205 epitope of tau. Three coronal levels (-8.04, -6.84, and -5.64 mm from bregma) were analysed at 4, 8, and 11-month post-inoculation. The main finding was that the animals inoculated with the tau fibrils displayed significantly greater amount of neurofibrillary changes and spread of tau fibrils, while such changes did not occur in animals inoculated with tau oligomers and phosphate buffer saline (controls). These findings suggest that tau fibrils may be the true culprit in AD and thus deserve further validation and a more detailed analysis in future studies.

Abstract (croatian)

Alzheimerova bolest (AB) je neurodegenerativna bolest i najčešći uzrok sindroma demencije. Postoje mnoge teorije o mogućim mehanizmima nastanka i širenja AB-a, od kojih je jedna tau hipoteza. Ta teorija pretpostavlja da hiperfosforilacija tau proteina dovodi do njihovog pogrešnog smatanja, oligomerizacije i nakupljanja, što remeti strukturu i funkciju mikrotubula te u konačnici odumiranja sinapsi i neurona. U ovom radu smo istražili promjene i širenje tau fibrila i tau oligomera inokuliranih u medijalni dio entorinalne moždane kore devet Wistar štakora. Za imunohistokemijsku vizualizaciju fosforiliranog tau proteina na epitopu Ser202/Thr205 korišteno je AT8 protutijelo. Tri koronalne razine (udaljenost od bregme -8,04, -6,84 i -5,64 mm) analizirane su 4, 8 i 11 mjeseci nakon inokulacije. Glavni nalaz je bio taj da su u životinjama kojima su inokulirane tau fibrile uočene značajne neurofibrilarne promjene i širenje tau fibrila, dok se takve promjene nisu dogodile kod životinja kojima su inokulirani tau oligomeri ili otopina fosfatnog pufera (kontrole). Navedeni rezultati upućuju da bi tau fibrile mogle biti uzročnik nastanka AB-a, pa stoga zaslužuju daljnju validaciju i detaljniju analizu u budućim istraživanjima.

• Keywords: Alzheimer’s Disease; Dementia; Immunohistochemistry; Tau Protein
• Keywords (english): Alzheimerova bolest; demencija; imunohistokemija; tau
• Language: english
• URN:NBN: urn:nbn:hr:217:244721
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra molekularne biologije (magistar/magistra molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access; Embargo expiration date: 2023-11-17
• Created on: 2021-11-22 13:59:32