Session 1H: Imaging Amyloid β Oligomers by molecular MRI: Diagnosing early-stage Alzheimer's disease

Session Number

Session 1H: 2nd Presentation

Advisor(s)

Drs. Kirsten Viola and Dr. William Klein, Northwestern University

Location

Room A117

Start Date

26-4-2018 9:40 AM

End Date

26-4-2018 10:25 AM

Abstract

Alzheimer’s disease is a neurodegenerative disorder characterized by deterioration of memory, visuospatial ability, and executive function. Neurodegeneration associated with Alzheimer’s disease is progressive and irreversible, and it is believed that long-term prognosis of patients would be significantly improved with an early diagnosis. Various diagnostic approaches have been developed, including those targeting amyloid fibrils, yet fibrils are not closely linked to the development of the disease. Amyloid-β oligomers are regarded as the putative initiators of disease pathogenesis, triggering tau pathology and instigating the neuronal damage that underlies dementia. Here, we report the development of a sensitive molecular magnetic resonance imaging (MRI) contrast probe that is specific for Aβ oligomers. The probe’s robust imaging signal is attributed to the coupling of an oligomer-specific targeting antibody to mixed metal magnetic nanostructures that yield enhanced contrast in MRI. Immunohistological analysis demonstrates that the probe is stable and detects Aβ oligomers on hippocampal cells and brain tissue. Intranasal administration of the probe to an Alzheimer’s disease mouse model revealed a pronounced, disease-dependent MRI signal in the hippocampus. The molecular MRI contrast probe shows potential as a freestanding diagnostic that targets Aβ oligomers to identify Alzheimer’s disease at its earliest stages when therapeutics are most potent.

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Apr 26th, 9:40 AM Apr 26th, 10:25 AM

Session 1H: Imaging Amyloid β Oligomers by molecular MRI: Diagnosing early-stage Alzheimer's disease

Room A117

Alzheimer’s disease is a neurodegenerative disorder characterized by deterioration of memory, visuospatial ability, and executive function. Neurodegeneration associated with Alzheimer’s disease is progressive and irreversible, and it is believed that long-term prognosis of patients would be significantly improved with an early diagnosis. Various diagnostic approaches have been developed, including those targeting amyloid fibrils, yet fibrils are not closely linked to the development of the disease. Amyloid-β oligomers are regarded as the putative initiators of disease pathogenesis, triggering tau pathology and instigating the neuronal damage that underlies dementia. Here, we report the development of a sensitive molecular magnetic resonance imaging (MRI) contrast probe that is specific for Aβ oligomers. The probe’s robust imaging signal is attributed to the coupling of an oligomer-specific targeting antibody to mixed metal magnetic nanostructures that yield enhanced contrast in MRI. Immunohistological analysis demonstrates that the probe is stable and detects Aβ oligomers on hippocampal cells and brain tissue. Intranasal administration of the probe to an Alzheimer’s disease mouse model revealed a pronounced, disease-dependent MRI signal in the hippocampus. The molecular MRI contrast probe shows potential as a freestanding diagnostic that targets Aβ oligomers to identify Alzheimer’s disease at its earliest stages when therapeutics are most potent.