Neuroimaging of Mouse Models of Alzheimer’s Disease

Jullienne, A.; Trinh, Michelle V.; Obenaus, André

doi:10.3390/biomedicines10020305

Cited by 16 publications

(20 citation statements)

References 227 publications

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“…One popular AD mouse model is the 3xTg-AD mouse, which was developed by combining mutant hAPP (Swedish), PSEN1 (MM146V), and tau (P301L) transgenes [ 19 ]. Like human AD, the 3xTg-AD mouse exhibits Aβ and tau pathologies with advancing age, coinciding with behavioral deficits (See [ 39 ]). Furthermore, emerging evidence, as seen with molecular biology [ 17 , 40 , 41 ] and cerebrovascular function [ 21 , 42 , 43 ], points to early development of dysregulated cerebral blood flow, vascular permeability, and angiogenesis in the 3xTg-AD mouse model.…”

Section: Discussionmentioning

confidence: 99%

Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease

et al. 2022

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Vascular dysfunction and structural abnormalities in Alzheimer’s disease (AD) are known to contribute to the progression of the pathology, and studies have tended to ignore the role of the vasculature in AD progression. We utilized the 3xTg-AD mouse model of AD to examine individual cerebral vessels and the cortical vascular network across the lifespan. Our vessel painting approach was used to label the entire cortical vasculature, followed by epifluorescence microscopy. The middle cerebral artery (MCA) tree was assessed with confocal microscopy, and a new method was developed to assess branching patterns as a measure of aging-related changes. We found that vascular remodeling was profoundly altered at 4–6 months of age, when the 3xTg-AD mouse is known to transition to cognitive impairment and Aβ deposition in both sexes. Analysis of vascular features (density, junctions, length) of the MCA territory highlighted sex-dependent differences across the 3xTg-AD mouse lifespan, with no alterations in branching patterns. Our current cerebrovascular angioarchitectural analyses demonstrate progressive alterations in individual cortical vessels, as well as in the vascular network of the cortex. These new findings advance our understanding of brain anatomy and physiology in the 3xTg-AD mouse, while potentially identifying unique diagnostic signatures of AD progression.

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Section: Discussionmentioning

confidence: 99%

Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease

et al. 2022

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“…In 5xFAD mice, amyloid plaques are first observed between two and four months of age in the cortical layer V and in the subiculum of the hippocampal formation ( Oblak et al, 2021 ). Different MRI techniques have been used to study the brain structure and function of 5xFAD mice ( Mlynarik et al, 2012 ; Igarashi et al, 2020 ; Jullienne et al, 2022 ). Manganese-enhanced MRI (MEMRI) has been utilized as an activity-dependent contrast agent.…”

Section: Introductionmentioning

confidence: 99%

Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging

Maharjan

Tsai²,

Lin³

et al. 2022

Front. Neurosci.

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PurposeTo evaluate the age-dependent microstructure changes in 5xFAD mice using high-resolution diffusion tensor imaging (DTI).MethodsThe 5xFAD mice at 4, 7.5, and 12 months and the wild-type controls at 4 months were scanned at 9.4T using a 3D echo-planar imaging (EPI) pulse sequence with the isotropic spatial resolution of 100 μm. The b-value was 3000 s/mm2 for all the diffusion MRI scans. The samples were also acquired with a gradient echo pulse sequence at 50 μm isotropic resolution. The microstructure changes were quantified with DTI metrics, including fractional anisotropy (FA) and mean diffusivity (MD). The conventional histology was performed to validate with MRI findings.ResultsThe FA values (p = 0.028) showed significant differences in the cortex between wild-type (WT) and 5xFAD mice at 4 months, while hippocampus, anterior commissure, corpus callosum, and fornix showed no significant differences for either FA and MD. FA values of 5xFAD mice gradually decreased in cortex (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) and fornix (0.140 ± 0.007 at 4 months, 0.132 ± 0.008 at 7.5 months, 0.126 ± 0.013 at 12 months) with aging. Both FA (p = 0.029) and MD (p = 0.037) demonstrated significant differences in corpus callosum between 4 and 12 months age old. FA and MD were not significantly different in the hippocampus or anterior commissure. The age-dependent microstructure alterations were better captured by FA when compared to MD.ConclusionFA showed higher sensitivity to monitor amyloid deposition in 5xFAD mice. DTI may be utilized as a sensitive biomarker to monitor beta-amyloid progression for preclinical studies.

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“…The NOR test is used to assess memory through novel and familiar object recognition [7]. The NOR test would be done following the Wan et al methodology, one day after the aerobic exercise was complete [10].…”

Section: Novel Object Recognition (Nor) Testmentioning

confidence: 99%

“…Many of the pathologic changes said to be associated with Aβ peptides and p-tau, can be visually seen, and confirmed through magnetic resonance imaging (MRI) [6]. MRI is a form of neuroimaging in which brain structure, volume and matter can be visualized as well as identified [7]. By using neuroimaging resources, such as MRI's, one can compare and contrast the physical features, that are said to be found in the AD brain, to the physical features that are associated with a healthy brain.…”

Section: Introductionmentioning

confidence: 99%

Exploring the Relation Between Aerobic Exercise, BDNF and Alzheimer’s Disease: A Research Protocol

Mahmood¹

2022

URNCST Journal

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Introduction: Alzheimer's Disease (AD) is a neurodegenerative disease that impacts the aging population by causing severe cognitive decline. Although there is no cure for AD, studies have shown that lifestyle changes may contribute to preventing AD. The purpose of this study is to investigate how regular exercise can influence a positive change in the cognitive decline that is associated with AD in rats, through a rise in BDNF levels. Methods: The study would be performed through a series of procedures and tests. Rats would be surgically induced with AD and separated into groups exposed to different aerobic exercise regiments. Then, they would either complete a novel object recognition test, to assess behavioural components, or magnetic resonance imaging, to assess structural components. Finally, they would have their brains extracted to measure protein levels. Results: The rats who would have been surgically induced with AD and exposed to regular exercise, are anticipated to have performed better on the novel object recognition test, than the rats surgically induced with AD, but not exposed to regular exercise. The rats who would have been surgically induced with AD and exposed to regular exercise, are anticipated to have shown greater gray matter and hippocampal volume on the magnetic resonance imaging, exhibit greater levels of BDNF, and show decreased levels of Aβ peptides and p-tau during the protein level measurement, than the rats induced with AD but not exposed to regular exercise. Discussion: The study would anticipate finding that the increased release of BDNF that occurs through regular exercise, decreases Aβ peptide and p-tau levels. Through decreasing Aβ peptide and p-tau levels, BDNF can be used as a form of neuroprotection in slowing down the cognitive decline that is associated with AD. Conclusion:The measures applied when researching ways in which the cognitive decline brought on by AD in rats can be reduced, could potentially be translated to further studying therapeutic treatments for AD in humans. These results could lead to similar preventative measures for other neurodegenerative diseases. Future directions may include informing the public of the importance that lifestyle changes may have on neurological health.

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Neuroimaging of Mouse Models of Alzheimer’s Disease

Cited by 16 publications

References 227 publications

Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease

Progressive Vascular Abnormalities in the Aging 3xTg-AD Mouse Model of Alzheimer’s Disease

Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging

Exploring the Relation Between Aerobic Exercise, BDNF and Alzheimer’s Disease: A Research Protocol

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