Detection of amyloid plaques targeted by USPIO-Aβ1–42 in Alzheimer's disease transgenic mice using magnetic resonance microimaging
Open accessAbstract
Amyloid plaques are one of the pathological hallmarks of Alzheimer's disease (AD). The visualization of amyloid plaques in the brain is important to monitor AD progression and to evaluate the efficacy of therapeutic interventions. Our group has developed several contrast agents to detect amyloid plaques in vivo using magnetic resonance microimaging (μMRI) in AD transgenic mice, where we used intra-carotid mannitol to enhance blood-brain barrier (BBB) permeability. In the present study, we used ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles, chemically coupled with Aβ1-42 peptide to detect amyloid deposition along with mannitol for in vivo μMRI by femoral intravenous injection. A 3D gradient multi-echo sequence was used for imaging with a 100μm isotropic resolution. The amyloid plaques detected by T2*-weighted μMRI were confirmed with matched histological sections. Furthermore, two different quantitative analyses were used. The region of interest-based quantitative measurement of T2* values showed contrast-injected APP/PS1 mice had significantly reduced T2* values compared to wild-type mice. In addition, the scans were examined with voxel-based morphometry (VBM) using statistical parametric mapping (SPM) for comparison of contrast-injected AD transgenic and wild-type mice. The regional differences seen in VBM comparing USPIO-Aβ1-42 injected APP/PS1 and wild-type mice correlated with the amyloid plaque distribution histologically, contrasting with no differences between the two groups of mice without contrast agent injection in regions of the brain with amyloid deposition. Our results demonstrated that both approaches were able to identify the differences between AD transgenic mice and wild-type mice, after injected with USPIO-Aβ1-42. The feasibility of using less invasive intravenous femoral injections for amyloid plaque detection in AD transgenic mice facilitates using this method for longitudinal studies in the pathogenesis of AD.
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Some studies co-injected mannitol or polyethylene glycol to transiently open the blood-brain barrier to amplify the abilities of USPIO coupled with Aβ(1-42) to detect Aβ in Alzheimer's disease model mice.
“Some studies have co-injected intravenously with mannitol or polyethylene glycol to transiently open the BBB to amplify the abilities of USPIO coupled with Aβ (1-42) to detect Aβ in AD model mice.[22][23]”
From Amyloid Plaque Imaging with a Targeted MRI Contrast Agent in a Transgenic Mouse Model of Alzheimer’s Disease (2022) · cites this paper as [23]
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- Zaim Wadghiri Y Sigurdsson EM Sadowski M Tang CY Aguilanldo JG Elliot JI Li Y Pappolla MA Duff K Turnbull D Wisniewski T 2003 Detection of Alzheimer's amyloid lesions in transgenic mice by magnetic resonance imaging Magnetic Resonance in Medicine 50 293 302 12876705
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“In most of the SPIO contrastmediated MRI studies, mannitol or high concentrated glucose solutions are used to deliver the contrast to the brain [30, 39].”
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- Authors
- Yang, J., Zaim Wadghiri, Y., Minh Hoang, D., Tsui, W., Sun, Y., Chung, E., Li, Y., Wang, A., de Leon, M., & Wisniewski, T.
- Affiliations
- NYU Langone Health (US)
- New York University (US)
- Ocean NanoTech (United States) (US)
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2011-04
- Volume
- 55
- Issue
- 4
- Pages
- 1600-1609
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC3085913
- OpenAlex
- W2013204605
- Cited by
- 135
- References
- 63
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 8 · 2022: 6 · 2021: 9 · 2020: 12 · 2019: 2 · 2018: 10 · 2017: 10 · 2016: 5 · 2015: 13 · 2014: 16 · 2013: 19 · 2012: 12
- FWCI
- 11.35
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- NeuroImage (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (AG20245, NS073502, AG008051, AG13616, AG12101, AG022373)
- American Health Assistance Foundation ADR (A2008-155)
- Alzheimer Association (08-91618)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Keywords
- amyloid plaques, Alzheimer's disease, APP/PS1 mice, T2-weighted imaging, blood-brain barrier permeability, mannitol, voxel-based morphometry, amyloid imaging
- MeSH terms
- Alzheimer Disease, Animals, Contrast Media, Dextrans, Magnetic Resonance Imaging, Mice, Inbred C57BL, Mice, Transgenic, Peptide Fragments, Sensitivity and Specificity, Reproducibility of Results, Amyloid beta-Peptides, Drug Delivery Systems, Mice, Magnetite Nanoparticles, Plaque, Amyloid
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