title: Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease.
abstract: One way to image the molecular pathology in Alzheimer's disease is by positron emission tomography using probes that target amyloid fibrils. However, these fibrils are not closely linked to the development of the disease. It is now thought that early-stage biomarkers that instigate memory loss are composed of Aβ oligomers. Here, we report a sensitive molecular magnetic resonance imaging contrast probe that is specific for Aβ oligomers. We attach oligomer-specific antibodies onto magnetic nanostructures and show that the complex is stable and binds to Aβ oligomers on cells and brain tissues to give a magnetic resonance imaging signal. When intranasally administered to an Alzheimer's disease mouse model, the probe readily reached hippocampal Aβ oligomers. In isolated samples of human brain tissue, we observed a magnetic resonance imaging signal that distinguished Alzheimer's disease from controls. Such nanostructures that target neurotoxic Aβ oligomers are potentially useful for evaluating the efficacy of new drugs and ultimately for early-stage Alzheimer's disease diagnosis and disease management.
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Kirsten L
authors.initials: KL
authors.lastname: Viola
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: James
authors.initials: J
authors.lastname: Sbarboro
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Ruchi
authors.initials: R
authors.lastname: Sureka
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Mrinmoy
authors.initials: M
authors.lastname: De
authors.affiliation: 1] Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA [2] Department of Pharmacology, Universidade Federal de Santa Catarina, Santa Catarina 88049900 Brazil.
authors.forename: Maíra A
authors.initials: MA
authors.lastname: Bicca
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Shaleen
authors.initials: S
authors.lastname: Vasavada
authors.affiliation: Illinois Math &Science Academy, Aurora, llinois 60506, USA.
authors.forename: Sreyesh
authors.initials: S
authors.lastname: Satpathy
authors.affiliation: Illinois Math &Science Academy, Aurora, llinois 60506, USA.
authors.forename: Summer
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Hrushikesh
authors.initials: H
authors.lastname: Joshi
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Pauline T
authors.initials: PT
authors.lastname: Velasco
authors.affiliation: Center for Advanced Molecular Imaging, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Keith
authors.initials: K
authors.lastname: MacRenaris
authors.affiliation: Center for Advanced Molecular Imaging, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: E Alex
authors.initials: EA
authors.lastname: Waters
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Chang
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Phan
authors.affiliation: Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Pascale
authors.initials: P
authors.lastname: Lacor
authors.affiliation: Department of Radiology, NorthShore University HealthSystems, Evanston, Illinois 60201, USA.
authors.forename: Pottumarthi
authors.initials: P
authors.lastname: Prasad
authors.affiliation: 1] Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois 60208, USA [2] International Institute for Nanotechnology (IIN), Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: Vinayak P
authors.initials: VP
authors.lastname: Dravid
authors.affiliation: 1] Department of Neurobiology, Northwestern University, Evanston, Illinois 60208, USA [2] International Institute for Nanotechnology (IIN), Northwestern University, Evanston, Illinois 60208, USA.
authors.forename: William L
authors.initials: WL
authors.lastname: Klein
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D003287:Contrast Media / Q000138:chemical synthesis; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D003287:Contrast Media