In vivo multi-parametric manganese-enhanced MRI for detecting amyloid plaques in rodent models of Alzheimer’s disease.
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Abstract
Abstract Amyloid plaques are a hallmark of Alzheimer’s disease (AD) that develop in its earliest stages. Thus, non-invasive detection of these plaques would be invaluable for diagnosis and the development and monitoring of treatments, but this remains a challenge due to their small size. Here, we investigated the utility of manganese-enhanced MRI (MEMRI) for visualizing plaques in transgenic rodent models of AD across two species: 5xFAD mice and TgF344-AD rats. Animals were given subcutaneous injections of MnCl 2 and imaged in vivo using a 9.4 T Bruker scanner. MnCl 2 improved signal-to-noise ratio but was not necessary to detect plaques in high-resolution images. Plaques were visible in all transgenic animals and no wild-types, and quantitative susceptibility mapping showed that they were more paramagnetic than the surrounding tissue. This, combined with beta-amyloid and iron staining, indicate that plaque MR visibility in both animal models was driven by plaque size and iron load. Longitudinal relaxation rate mapping revealed increased manganese uptake in brain regions of high plaque burden in transgenic animals compared to their wild-type littermates. This was limited to the rhinencephalon in the TgF344-AD rats, while it was most significantly increased in the cortex of the 5xFAD mice. Alizarin Red staining suggests that manganese bound to plaques in 5xFAD mice but not in TgF344-AD rats. Multi-parametric MEMRI is a simple, viable method for detecting amyloid plaques in rodent models of AD. Manganese-induced signal enhancement can enable higher-resolution imaging, which is key to visualizing these small amyloid deposits. We also present the first in vivo evidence of manganese as a potential targeted contrast agent for imaging plaques in the 5xFAD model of AD.
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The MRI signal has been enhanced by MEMRI to visualize Aβ plaques in transgenic rodent models of AD.
“The MRI signal has been enhanced by the MEMRI to visualize the Aβ plaques in transgenic rodent models of AD (Kim et al., 2021).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Kim et al., 2021
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- Authors
- Kim, E., Di Censo, D., Baraldo, M., Simmons, C., Rosa, I., Randall, K., Ballard, C., Dickie, B. R., Williams, S. C. R., Killick, R., & Cash, D.
- Affiliations
- King's College London (GB)
- University of L'Aquila (IT)
- University of Exeter (GB)
- Manchester Academic Health Science Centre (GB)
- Corresponding author
- Kim, Eugene
- ORCID
- Venue
- Scientific Reports
- Published
- 2021-06-14
- Volume
- 11
- Issue
- 1
- Pages
- 12419-12419
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC8203664
- OpenAlex
- W3168299968
- Cited by
- 15
- References
- 47
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 4 · 2022: 3 · 2021: 1
- FWCI
- 1.57
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Alzheimer's Society (AS-PhD-18B-015)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- manganese-enhanced MRI, amyloid plaques, Alzheimer's disease, 5xFAD mice, TgF344-AD rats, manganese chloride, quantitative susceptibility mapping, amyloid-beta, rhinencephalon, transgenic rodent models
- MeSH terms
- Multiparametric Magnetic Resonance Imaging, Alzheimer Disease, Animals, Cerebral Cortex, Chlorides, Disease Models, Animal, Female, Humans, Injections, Subcutaneous, Iron, Male, Mice, Transgenic, Amyloid beta-Peptides, Manganese Compounds, Mice, Rats, Rats, Transgenic, Plaque, Amyloid
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