Event Title

Development of an Antibody-Targeted PET Probe for Early Diagnostic Imaging of Alzheimer's Disease

Session Number

Q02

Advisor(s)

Erika Cline, Northwestern University
William Klein, Northwestern University
Kirsten Viola, Northwestern University

Location

A-123

Start Date

28-4-2016 1:35 PM

End Date

28-4-2016 2:00 PM

Disciplines

Neuroscience and Neurobiology

Abstract

There currently exist no methods to diagnose Alzheimer’s Disease (AD), which is the most common neurodegenerative disease characterized by progressive mental deterioration. The molecular focus on AD is shifting away from amyloid plaques and towards their peptide form- the amyloid-β oligomer (AβO). The pathology of AβOs and downstream tau more closely correlate with neuronal loss in comparison to amyloid plaques and have only been found in demented individuals, suggesting that AβOs initiate AD pathogenesis. We selected NU4 as our high-affinity, therapeutic antibody to direct our probe towards the desired target. In this study, we concluded that NU4 labels pathology distinct from traditional plaque stains and that NU4-DOTA retains its immunoreactivity to AβOs in vitro. Mice injected with NU4PET displayed a robust AD-dependent signal. The PET signal correlated with fluorescent intensity detected using immunofluorescent analysis. Human brains labeled with NU4 demonstrated pathology similar to that seen in mice, suggesting that mouse-derived NU4 can be used to target AβOs in humans. A study comparing age and sex dependence on AβO levels demonstrated that AβOs are present at 2 months of age in 5xFAD mice, 2-3 months before the onset of dementia. Conclusively, NU4PET demonstrates tremendous potential as an early diagnostic agent for AD.


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Apr 28th, 1:35 PM Apr 28th, 2:00 PM

Development of an Antibody-Targeted PET Probe for Early Diagnostic Imaging of Alzheimer's Disease

A-123

There currently exist no methods to diagnose Alzheimer’s Disease (AD), which is the most common neurodegenerative disease characterized by progressive mental deterioration. The molecular focus on AD is shifting away from amyloid plaques and towards their peptide form- the amyloid-β oligomer (AβO). The pathology of AβOs and downstream tau more closely correlate with neuronal loss in comparison to amyloid plaques and have only been found in demented individuals, suggesting that AβOs initiate AD pathogenesis. We selected NU4 as our high-affinity, therapeutic antibody to direct our probe towards the desired target. In this study, we concluded that NU4 labels pathology distinct from traditional plaque stains and that NU4-DOTA retains its immunoreactivity to AβOs in vitro. Mice injected with NU4PET displayed a robust AD-dependent signal. The PET signal correlated with fluorescent intensity detected using immunofluorescent analysis. Human brains labeled with NU4 demonstrated pathology similar to that seen in mice, suggesting that mouse-derived NU4 can be used to target AβOs in humans. A study comparing age and sex dependence on AβO levels demonstrated that AβOs are present at 2 months of age in 5xFAD mice, 2-3 months before the onset of dementia. Conclusively, NU4PET demonstrates tremendous potential as an early diagnostic agent for AD.