Synaptic health in Alzheimer’s Disease: exploring MEG, MRI, and neuropathology

Thesis

Alzheimer's disease (AD) is a neurodegenerative disorder marked by cognitive decline and neuropathological features, including amyloid plaques and tau tangles. Early detection and monitoring are crucial for future interventions, especially given the lack of effective treatments. Traditional biomarkers like PET and lumbar puncture are invasive and do not capture the dynamic functional changes associated with the disease. This thesis explores the potential of Magnetoencephalography (MEG) as a non-invasive biomarker for AD, focusing on synaptic brain health, cognition, and neuropathology.

Utilizing the New Therapeutics in Alzheimer's Disease (NTAD) cohort, comprising biomarker- positive patients and biomarker-negative controls, I investigated resting-state MEG data. Distinct spectral patterns were observed in the eyes-open and eyes-closed conditions. In the eyes-open condition, patients exhibited increased theta activity, decreased alpha/beta activity, and a shift in alpha peak frequency. In the eyes-closed condition, there was an increase in theta activity, a shift in alpha peak frequency, and a decrease in alpha peak amplitude. Test-retest reliability was good to excellent in higher frequency bands, with the eyes-open condition showing better reliability across more sensors. Pathological analysis revealed associations between alpha peak frequency and amyloid/tau and p-tau levels. Both clinical and research- based cognitive tests were significantly associated with the MEG findings. fMRI analysis revealed differences in resting-state networks, including the Default Mode Network (DMN), with distinct relationships to neuropathology and neuropsychological measures. An exploratory analysis comparing MEG and fMRI metrics suggested that MEG may be more closely related to early AD brain alterations.

Overall, these findings provide insights into the potential use of MEG as a biomarker for AD, with the resting-state eyes-open condition emerging as the most reliable. The work contributes to the understanding of how MEG can be applied clinically in AD research, advancing its potential for monitoring disease progression, and informing therapeutic interventions.

Authors: Pitt , J

• DOI: 10.5287/ora-yjzjoovvg
• Type of award: DPhil
• Level of award: Doctoral
• Awarding institution: University of Oxford
• Language: English
• Keywords: MEG; neuropathology; Alzheimer's disease
• Subjects: Alzheimer's disease