Investigation of the potential role of oral pathogens in Parkinson's Disease

Student thesis: Master's ThesisMaster of Science by Research (MScR)

Abstract

Introduction:
Parkinson’s disease (PD) is a progressive neurodegenerative disease, characterised by motor symptoms which are caused by loss of dopaminergic neurons in the substantia nigra (Pradeep et al., 2015; Chen et al., 2017).
Misfolded protein aggregations, mainly comprised of α-synuclein accumulations in PD brains are termed Lewy Bodies (LB) (Outeiro et al., 2019), with LB progression being identified in six stages (Braak et al., 2003). α-synuclein has been found to have antimicrobial properties (Park et al., 2016), and recently questions have been raised as to whether spread of α-synuclein is a response to infection, and whether peripheral infections such as periodontitis could be a risk factor for PD (Ferrari and Tarelli, 2011).
Here, post-mortem PD brain tissue was analysed for presence and abundance of bacterial species compared with controls (C). Presence of α-synuclein has also been investigated to analyse any differences between PD and C.
Methods:
Ten PD and ten C brain tissues were obtained from the South West Dementia Brain Bank (SWDBB). DNA extraction was performed, and concentrations determined. Using quantitative polymerase chain reaction (qPCR) to amplify variable 3 and 4 region of 16S rRNA gene, bacterial DNA was quantified against known standards. PCR product was sent for Next Generation Sequencing (NGS) to determine taxa present in samples. Immunoassays were used to determine α-synuclein concentrations and compared with bacterial concentrations to determine any correlation.
Results:
Higher bacterial concentrations were found in PD brains than C, in particular the midbrain areas. There was no correlation between bacterial and α-synuclein concentration. Seven of the top ten genera identified by NGS were found to be oral, and Prevotella denticola, a known pathogen in periodontitis, the most differentially represented species between control and PD in substantia nigra brain area samples, with it being represented significantly more in PD samples (p
Date of Award21 Mar 2023
Original languageEnglish
Awarding Institution
  • University of Bristol
SupervisorNicola X West (Supervisor) & Shelley J Allen Allen-Birt (Supervisor)

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