Date of Award
Doctor of Philosophy (PhD)
Alzheimer disease is one of the deadliest and most expensive diseases in the United States. Knowing whether a family member has Alzheimer disease may help households better plan for health-related expenses. However, fewer than half of primary care physicians report being comfortable diagnosing cognitive impairment due to Alzheimer disease. One solution is to supplement cognitive assessments with biomarkers to track abnormal levels of amyloid-β and tau, the pathological hallmarks of Alzheimer disease. Among these, positron emission tomography (PET) has emerged as an established standard that other biomarkers are compared to. However, as PET imaging moves from being used in research settings to clinical settings, its reliability must be established once more under these new conditions. In this dissertation, I aim to ascertain scientific reliability in PET imaging for Alzheimer disease as the technology moves from being used as a quantitative measure to being used for visual reads (Chapter 1, published as Chen, C.D. et al., Comparing tau PET visual interpretation with tau PET quantification, CSF biomarkers, and longitudinal clinical assessment, Journal of Alzheimer’s Disease, 2023); from being used in patients with late-onset Alzheimer disease to patients with rare, dominantly inherited forms of Alzheimer disease (Chapter 2, published as Chen, C.D. et al., Ante- and postmortem tau in autosomal dominant and late-onset Alzheimer’s disease, Annals of Clinical and Translational Neurology, 2020 and Chapter 3, published as Chen, C.D. et al., Comparing amyloid-β plaque burden with antemortem PiB PET in autosomal dominant and late-onset Alzheimer disease, Acta Neuropathologica, 2021); and from being used for tracking disease progression in observational studies to tracking treatment effects in clinical trials (Chapter 4, published as Chen, C.D. et al., Longitudinal head-to-head comparison of 11C-PiB and 18F-florbetapir in a Phase 2/3 clinical trial of anti-amyloid-β monoclonal antibodies in dominantly inherited Alzheimer disease, European Journal of Nuclear Medicine and Molecular Imaging, 2023).
Tammie L. Benzinger
Janine D. Bijsterbosch, Abhinav K. Jha, Richard J. Perrin, Aristeidis Sotiras,