Cited by 33Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

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Neuroimaging of Mouse Models of Alzheimer’s Disease

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Jullienne, Amandine, Trinh, Michelle V., Obenaus, Andre·2022·Biomedicines

DOI 10.3390/biomedicines10020305PMC PMC8869427

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Abstract

Magnetic resonance imaging (MRI) and positron emission tomography (PET) have made great strides in the diagnosis and our understanding of Alzheimer’s Disease (AD). Despite the knowledge gained from human studies, mouse models have and continue to play an important role in deciphering the cellular and molecular evolution of AD. MRI and PET are now being increasingly used to investigate neuroimaging features in mouse models and provide the basis for rapid translation to the clinical setting. Here, we provide an overview of the human MRI and PET imaging landscape as a prelude to an in-depth review of preclinical imaging in mice. A broad range of mouse models recapitulate certain aspects of the human AD, but no single model simulates the human disease spectrum. We focused on the two of the most popular mouse models, the 3xTg-AD and the 5xFAD models, and we summarized all known published MRI and PET imaging data, including contrasting findings. The goal of this review is to provide the reader with broad framework to guide future studies in existing and future mouse models of AD. We also highlight aspects of MRI and PET imaging that could be improved to increase rigor and reproducibility in future imaging studies.

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Figure 1 Pubmed citations for 5xFAD and 3xTg-AD mouse models. (a) The total number of Pubmed citations for the two most popular AD mouse models, illustrates the rapid rise in reports utilizing the 5xFAD compared to the 3xTg-AD mouse models of AD. (b) When the Pubmed search criteria were further refined to only 5xFAD or 3xTg-AD with MRI, the number of citations dropped precipitously. Again, the 5xFAD mouse model has an increased utilization in neuroimaging studies (Pubmed search “5xFAD” or “3xTg” and then combined with “magnetic resonance imaging”).CC BY · PubMed Central

Figure 2 WT and transgenic female mice histological staining. (a) Staining in 5xFAD females at 18 months of age demonstrated a high load of β-amyloid plaques (Thioflavin-S) throughout the brain accompanied by elevated microglial activation (IBA-1) that was not observed in WT mice. (b) Staining for human Tau (HT7) as well as β-amyloid plaques (Thioflavin-S) in 18-month-old 3xTg-AD females revealed a more focal staining pattern compared to the 5xFAD model at the same age. Note the relative absence of β-amyloid plaques in the 3xTg-AD mice. Scale bar = 1 mm. (Images courtesy of K. Green, UCI MODEL-AD Consortium).CC BY · PubMed Central

Figure 3 Diffusion magnetic resonance imaging (dMRI) in 12-month-old female mice. Diffusion tensor imaging (DTI) parametric maps for axial diffusivity (AxD), radial diffusivity (RD), mean diffusivity (MD), fractional anisotropy (FA) and colored FA in females WT and 5xFAD at 12 months of age. Exemplar images at the level of the dorsal hippocampus illustrate changes in the corpus callosum and within the hippocampus.CC BY · PubMed Central

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Evaluation of the neuroprotective effect of taurine in Alzheimer’s disease using functional molecular imaging
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Microstructural White Matter Alterations in Mild Cognitive Impairment and Alzheimer’s Disease
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Diffusion Magnetic Resonance Imaging-Based Biomarkers for Neurodegenerative Diseases
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White matter alterations in early‐stage Alzheimer's disease: A tract‐specific study
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In vivo imaging of tau pathology using multi-parametric quantitative MRI
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In vivo Imaging of Glial Activation in Alzheimer's Disease
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Age-Dependent Impairment of Somatosensory Response in the Amyloid Precursor Protein 23 Transgenic Mouse Model of Alzheimer's Disease
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Longitudinal assessment of Alzheimer's β‐amyloid plaque development in transgenic mice monitored by in vivo magnetic resonance microimaging
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Role of Myo-Inositol by Magnetic Resonance Spectroscopy in Early Diagnosis of Alzheimer’s Disease in APP/PS1 Transgenic Mice
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A multicenter 1 H-MRS study of the medial temporal lobe in AD and MCI
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Gray and white matter degeneration revealed by diffusion in an Alzheimer mouse model
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Impaired Eyeblink Conditioning and Decreased Hippocampal Volume in PDAPP V717F Mice
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Ensemble Classification of Alzheimer's Disease and Mild Cognitive Impairment Based on Complex Graph Measures from Diffusion Tensor Images
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Volumetric MRI and MRS provide sensitive measures of Alzheimer's disease neuropathology in inducible Tau transgenic mice (rTg4510)
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A longitudinal multimodal in vivo molecular imaging study of the 3xTg-AD mouse model shows progressive early hippocampal and taurine loss
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Cortical atrophy and hypoperfusion in a transgenic mouse model of Alzheimer's disease
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Magnetic resonance angiography and vascular corrosion casting as tools in biomedical research: application to transgenic mice modeling Alzheimer's disease
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Inhibition of Colony-Stimulating Factor 1 Receptor by PLX3397 Prevents Amyloid Beta Pathology and Rescues Dopaminergic Signaling in Aging 5xFAD Mice
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Proton and Phosphorus Magnetic Resonance Spectroscopy of a Mouse Model of Alzheimer's Disease
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Diffusion kurtosis imaging to detect amyloidosis in an APP/PS1 mouse model for Alzheimer's disease
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The human hippocampus and its subfield volumes across age, sex and APOE e4 status
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Early stage alterations in white matter and decreased functional interhemispheric hippocampal connectivity in the 3xTg mouse model of Alzheimer’s disease.
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Complex interplay between brain function and structure during cerebral amyloidosis in APP transgenic mouse strains revealed by multi-parametric MRI comparison
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Self-citation
Remote sites of structural atrophy predict later amyloid formation in a mouse model of Alzheimer's disease
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Sex- and age-specific modulation of brain GABA levels in a mouse model of Alzheimer's disease
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Long-term Dantrolene Treatment Reduced Intraneuronal Amyloid in Aged Alzheimer Triple Transgenic Mice
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Spatial learning and memory impairments are associated with increased neuronal activity in 5XFAD mouse as measured by manganese-enhanced magnetic resonance imaging
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Deficits in axonal transport in hippocampal-based circuitry and the visual pathway in APP knock-out animals witnessed by manganese enhanced MRI
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Regional metabolic alteration of Alzheimer's disease in mouse brain expressing mutant human APP-PS1 by 1H HR-MAS☆
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Small-Animal PET Imaging of Tau Pathology with 18F-THK5117 in 2 Transgenic Mouse Models
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Monitoring blood flow alterations in the Tg2576 mouse model of Alzheimer's disease by in vivo magnetic resonance angiography at 17.6T
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Differential MRI patterns of brain atrophy in double or single transgenic mice for APP and/or SOD
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Neurite orientation dispersion and density imaging reveals white matter and hippocampal microstructure changes produced by Interleukin-6 in the TgCRND8 mouse model of amyloidosis
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A stereotaxic MRI template set of mouse brain with fine sub-anatomical delineations: Application to MEMRI studies of 5XFAD mice
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The fornix provides multiple biomarkers to characterize circuit disruption in a mouse model of Alzheimer’s disease.
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Authors: Jullienne, A., Trinh, M. V., & Obenaus, A.
Affiliations: University of California, Irvine (US)
Department of Pediatrics, University of California, Irvine, CA 92697, USA
ORCID: Jullienne, Amandine
Obenaus, Andre
Venue: Biomedicines
Publisher: MDPI AG
Published: 2022-01-28
Volume: 10
Issue: 2
Pages: 305
ISSN: 2227-9059 (ISSN-L)
DOI: 10.3390/biomedicines10020305
PMC: PMC8869427
OpenAlex: W4210462365
Cited by: 32
References: 232
Citations by year: 2026: 8 · 2025: 8 · 2024: 6 · 2023: 6 · 2022: 4
FWCI: 0.83
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Biomedicines (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
eScholarship (California Digital Library) (submittedVersion, cc-by)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: National Institute on Aging (AG054345-01, AG054349-01)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: Alzheimer's disease, mouse models of Alzheimer's disease, 3xTg-AD mice, 5xFAD mice, magnetic resonance imaging, positron emission tomography, imaging biomarkers

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Neuroimaging of Mouse Models of Alzheimer’s Disease

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