Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

Kirsten L. Viola; James Sbarboro; Ruchi Sureka; Mrinmoy De; Maíra A. Bicca; Jane Wang; Shaleen Vasavada; Sreyesh Satpathy; Summer Wu; Hrushikesh Joshi; Pauline T. Velasco; Keith Macrenaris; E. Alex Waters; Chang Lu; Joseph Phan; Pascale Lacor; Pottumarthi Prasad; Vinayak P. Dravid; William L. Klein

doi:10.1038/nnano.2014.254

Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

Kirsten L. Viola, James Sbarboro, Ruchi Sureka, Mrinmoy De, Maíra A. Bicca, Jane Wang, Shaleen Vasavada, Sreyesh Satpathy, Summer Wu, Hrushikesh Joshi, Pauline T. Velasco, Keith Macrenaris, E. Alex Waters, Chang Lu, Joseph Phan, Pascale Lacor, Pottumarthi Prasad, Vinayak P. Dravid, William L. Klein^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

165 Scopus citations

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.

Original language	English (US)
Pages (from-to)	91-98
Number of pages	8
Journal	Nature nanotechnology
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/nnano.2014.254
State	Published - Jan 1 2015

ASJC Scopus subject areas

Bioengineering
Atomic and Molecular Physics, and Optics
Biomedical Engineering
General Materials Science
Condensed Matter Physics
Electrical and Electronic Engineering

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/nnano.2014.254

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Viola, K. L., Sbarboro, J., Sureka, R., De, M., Bicca, M. A., Wang, J., Vasavada, S., Satpathy, S., Wu, S., Joshi, H., Velasco, P. T., Macrenaris, K., Waters, E. A., Lu, C., Phan, J., Lacor, P., Prasad, P., Dravid, V. P., & Klein, W. L. (2015). Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease. Nature nanotechnology, 10(1), 91-98. https://doi.org/10.1038/nnano.2014.254

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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.",

author = "Viola, {Kirsten L.} and James Sbarboro and Ruchi Sureka and Mrinmoy De and Bicca, {Ma{\'i}ra A.} and Jane Wang and Shaleen Vasavada and Sreyesh Satpathy and Summer Wu and Hrushikesh Joshi and Velasco, {Pauline T.} and Keith Macrenaris and Waters, {E. Alex} and Chang Lu and Joseph Phan and Pascale Lacor and Pottumarthi Prasad and Dravid, {Vinayak P.} and Klein, {William L.}",

note = "Funding Information: The authors thank the staff of the Biological Imaging Facility (BIF), the Center for Advanced Molecular Imaging (CAMI) and Northwestern University{\textquoteright}s Atomic and Nanoscale Characterization Experimental Center (NUANCE) at Northwestern University, and the Department of Radiology at NorthShore University HealthSystems. The authors also thank the Northwestern Brain Bank at the Cognitive Neurology and Alzheimer{\textquoteright}s Disease Center (CNADC) for providing the human Alzheimer{\textquoteright}s disease and control brain tissue. The authors acknowledge support from their funding agencies and grants. This work was funded by the National Institutes of Health (AG022547, AG029460 and AG045637 to W.L.K.), by Baxter Healthcare (to W.L.K.) and partially by the National Institutes of Health–Centers of Cancer Nanotechnology Excellence through the Nanoconstruct Core (award U54CA119341 to V.P.D., H.J. and M.D.) Publisher Copyright: {\textcopyright} 2015 Macmillan Publishers Limited.",

year = "2015",

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doi = "10.1038/nnano.2014.254",

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Viola, KL, Sbarboro, J, Sureka, R, De, M, Bicca, MA, Wang, J, Vasavada, S, Satpathy, S, Wu, S, Joshi, H, Velasco, PT, Macrenaris, K, Waters, EA, Lu, C, Phan, J, Lacor, P, Prasad, P, Dravid, VP & Klein, WL 2015, 'Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease', Nature nanotechnology, vol. 10, no. 1, pp. 91-98. https://doi.org/10.1038/nnano.2014.254

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AU - Viola, Kirsten L.

AU - Sbarboro, James

AU - Sureka, Ruchi

AU - De, Mrinmoy

AU - Bicca, Maíra A.

AU - Wang, Jane

AU - Vasavada, Shaleen

AU - Satpathy, Sreyesh

AU - Wu, Summer

AU - Joshi, Hrushikesh

AU - Velasco, Pauline T.

AU - Macrenaris, Keith

AU - Waters, E. Alex

AU - Lu, Chang

AU - Phan, Joseph

AU - Lacor, Pascale

AU - Prasad, Pottumarthi

AU - Dravid, Vinayak P.

AU - Klein, William L.

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Towards non-invasive diagnostic imaging of early-stage Alzheimer's disease

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