Indiana University-Purdue University Indianapolis (IUPUI) / Neuroimaging biomarkers play a crucial role in our understanding of
Alzheimer’s disease. Beyond providing a fast and accurate in vivo picture of the
neuronal structure and biochemistry, these biomarkers make up a research
framework, defined in a 2018 as the A(amyloid)/T(tau)/N(neurodegeneration)
framework after three of the hallmarks of Alzheimer’s disease. I first used
imaging measures of amyloid, tau and neurodegeneration to study clinically
diagnosed Alzheimer’s disease. After dividing subjects into early (onset younger
than 65) and late-onset (onset of 65 and older) amyloid-positive (AD) and
amyloid-negative (nonAD) groups, I saw radically differing topographical
distribution of tau and neurodegeneration. AD subjects with an early disease
onset had a much more severe amyloid, tau and neurodegeneration than lateonset
AD. In the nonAD group, neurodegeneration was found only in early-onset
FDG PET data and in a nonAlzheimer’s-like MRI and FDG pattern for late-onset.
The late-onset nonAD resembled that of limbic-predominant age-related TDP-43
encephalopathy.
I next utilized an imaging genetics approach to associate genome-wide
significant Alzheimer’s risk variants to structural (MRI), metabolic (FDG PET) and
tau (tau PET) imaging biomarkers. Linear regression was used to select variants
for each of the models and included a pooled sample, cognitively normal, mild
cognitive impairment and dementia groups in order to fully capture the cognitive
spectrum from normal cognition to the most severely impaired. Model selected
variants were replicated using voxelwise regression in an exploratory analysis of
spatial associations for each modality. For each imaging type, I replicated some
associations to the biomarkers previously seen, as well as identified several
novel associations. Several variants identified with crucial Alzheimer’s
biomarkers may be potential future targets for drug interventions.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/23683 |
| Date | 08 1900 |
| Creators | Stage, Edwin Carl Jr. |
| Contributors | Yoder, Karmen K., Apostolova, Liana G., Risacher, Shannon L., Gao, Sujuan, Saykin, Andrew J. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | en_US |
| Detected Language | English |
| Type | Dissertation |
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