Huber, BertrandKüreli, GülceAntinew, Precious Dominique M.2025-09-232025-09-232024https://hdl.handle.net/2144/512912024Alzheimer’s disease (AD) and chronic traumatic encephalopathy (CTE) are two of the most common neurodegenerative diseases with overlapping symptoms including cognitive dysfunction and dementia. The primary hallmark of AD is the presence of extracellular neuritic plaques composed of amyloid-beta (Aβ) and neurofibrillary tangle (NFTs) which are aggregates of insoluble tau proteins. CTE pathology is characterized by the widespread deposition of hyperphosphorylated tau (p-tau). The golden standard to fully establish the diagnosis of AD and CTE are through post-mortem examination and staining. The Braak staging of AD and McKee staging of CTE are often used to determine the severity of p-tau pathology. White matter (WM) changes are also involved in the progression of neurodegenerative diseases. WM is composed of myelin that is responsible for facilitating communication between different regions of the brain. Damages to myelin contributes significantly to the progression and pathology of neurodegenerative diseases. In this study, we aim to investigate the role of myelin pathology in AD and CTE. We also aim to establish a comparative analysis of the distribution of neuropathological biomarkers. We investigated a total of 14 postmortem brain samples of the dorsolateral frontal cortex and divided into three cohorts: normal control (NC), AD and CTE. Inclusion criteria consisted of sex, age, PMI, years played of contact sports, McKee stage and/or Braak stage. Tissue blocks were imaged using CCP-BRM techniques to image myelin and were stained using AT8 and Ab4G8 antibodies to detect p-tau and Aβ. Our results showed that CTE had the most myelin defect compared to NC and AD groups. AD had the highest proportion of NFTs and Aβ stained area. We also observed that there is statistically significant correlation between myelin defect count to AT8/Ab4G8 stained percent area (p<0.001, p=0.002). We conclude that CTE having a heightened prevalence of myelin defect may indicate that it has a unique pathological signature exclusive to CTE. Furthermore, previous literature has stated a reciprocal relationship between the presence of toxic pathological products and myelin damage. We did not find significantly strong correlations between these parameters, suggesting there may be more complex pathophysiological changes occurring. While our study contributes to the current understanding of myelin pathology in neurodegenerative diseases, there remains much to unravel regarding the neuropathological changes underlying AD and CTE. Further research is necessary to uncover the many factors behind these diseases and to devise specific methods for diagnosing, treating, and ultimately preventing them.en-USNeurosciencesAlzheimer's diseaseAmyloidChronic traumatic encephalopathyMyeinTauThesis/Dissertation2025-09-22