Imaging and Genetics of Two Amyloid Related Diseases: Alzheimer’s Disease and Down Syndrome

Abstract

Alzheimer’s Disease is an irreversible, degenerative disease of the brain that accounts for a majority of dementia cases each year, in both the general population and in patients with Down Syndrome. The advancement of in vivo imaging modalities that detect the neuropathologies associated with both Down Syndrome and Alzheimer’s Disease present new opportunities to explore these diseases in living human subjects. Imaging biomarkers not only permit earlier, more accurate patient diagnosis, but quantitative, neuropathology-based traits derived from imaging modalities offer increased power to detect associations with large-scale genetic data. This field of investigation has been termed “imaging genetics”. Imaging genetics studies aim to identify novel risk genes and elucidate gene function and novel mechanisms of disease pathology and etiology. In this dissertation, I have conducted imaging genetics studies of the neuropathologies of Alzheimer’s Disease and Down Syndrome in order to increase our understanding of the genetic etiology underlying these pathologies. Furthermore, new biomarkers of these pathologies are still needed. Thus, a magnetic resonance imaging sequence which has been shown to detect amyloid beta plaque in mice is explored in human studies in this dissertation. This work contributes novel findings to the body of research aimed at early identification of patients at risk of Alzheimer’s Disease.