Thesis
Depth-resolved fibre photometry for Alzheimer’s disease plaque pathology in vivo
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2024
- Thesis identifier
- T16915
- Person Identifier (Local)
- 202156165
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- The progression of potential Alzheimer’s disease (AD) treatments to the clinic may be hindered by the pre-clinical screening approach used to access plaque-modifying effects in vivo. Specifically, these approaches generally lack real-time assessment across deep brain regions due to a lack of technology permitting this, leaving vital information overlooked. We investigate whether using fibre photometry with a tapered optical fibre allows in vivo real-time, depth-resolved monitoring of plaques in freely behaving AD mouse models. Thereby, allowing investigation of plaque modifications caused by potential AD treatments. First, to confirm feasibility of this approach, we labelled plaques using a peripherally administered blood-brain-barrier-permeable plaque marker, Methoxy-x04, and performed fibre photometry with a conventional flat fibre across brain regions of 5xFAD mice. We confirmed significant correlation between in vivo photometry and post-mortem histological plaque signals, indicating that fibre photometry is a feasible approach to assess plaque pathology. Then, we adopted tapered fibres to realise real-time, depth-resolved photometry in freely behaving 5xFAD mice. We observed a steady increase of in vivo fluorescence from 30-minutes after Methoxy-x04 injection, and consistently increased fluorescence when redosing Methoxy-x04 at 24-h intervals, showing greater fluorescence at regions with high plaque load. Next, to examine the efficacy of a non-invasive treatment approach, mice were exposed to 1-hour of 40-Hz sensory stimulation while monitoring plaque pathology. Electrophysiological signals show increased 40-Hz power in cortical and hippocampal regions, in a stimulus-dependent manner. However, 40-Hz treatment resulted in no significant change in plaque pathology detected by tapered fibre photometry or histology. Overall, for the first time, we have shown real-time, depth-resolved assessment of AD plaque pathology in freely behaving mice. While further study is required to confirm the effect of 40-Hz treatment, this novel approach can accelerate prospective treatments to the clinic and be an integral tool for investigating the multifactorial complexity of AD.
- Advisor / supervisor
- Sakata, Shuzo
- Resource Type
- DOI
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PDF of thesis T16915 | 2024-05-13 | Público | Descargar |