Quantitative evaluation of MRI and histological characteristics of the 5xFAD Alzheimer mouse brain

Spencer, Nicholas G.; Bridges, Leslie; Elderfield, Kay; Amir, K.; Austen, Brian; Howe, Franklyn A.

doi:10.1016/j.neuroimage.2013.02.071

Cited by 24 publications

(28 citation statements)

References 34 publications

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“…Such abnormality in visual and visual association areas may also underpin the clinical and cognitive impairments in patients with DLB, such as recurrent visual hallucinations and visuo-perceptual dysfunction. Consistent with our finding, decreased qT1 is also associated with the layer specific increase in b-amyloid deposition in 5xFAD mice [18].…”

Section: Discussionsupporting

confidence: 92%

“…For example, significant variations in these parameters were found during aging [17] and underlying physiological processes at the cellular and molecular level demonstrated by postmortem histological investigations in transgenic 5xFAD mouse animal model of AD [18]. We therefore hypothesize that quantitative qT1 and qT2 mapping is able to differentiate DLB from healthy controls and indirectly reveal neurobiological abnormalities of DLB at subvoxel scale.…”

Section: Introductionmentioning

confidence: 90%

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Tissue microstructural changes in dementia with Lewy bodies revealed by quantitative MRI

Blamire

Watson

et al. 2014

J Neurol

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We aimed to characterize dementia with Lewy bodies (DLB) by the quantitative MRI parameters of longitudinal relaxation time (qT1) and transverse relaxation time (qT2). These parameters reflect potential pathological changes in tissue microstructures, which may be detectable noninvasively in brain areas without evident atrophy, so may have potential value in revealing the early neuropathological changes in DLB. We conducted a cross-sectional study of subjects with DLB (N = 35) and similarly aged control participants (N = 35). All subjects underwent a detailed clinical and neuropsychological assessment and structural and quantitative 3T MRI. Quantitative MRI maps were obtained using relaxation time mapping methods. Statistical analysis was performed on gray matter qT1 and qT2 values. We found significant alterations of quantitative parameters in DLB compared to controls. In particular, qT1 decreases in bilateral temporal lobes, right parietal lobes, basal ganglia including left putamen, left caudate nucleus and left amygdala, and left hippocampus/parahippocampus; qT2 decreases in left putamen and increases in left precuneus. These regions showed only partial overlap with areas where grey matter loss was found, making atrophy an unlikely explanation for our results. Our findings support that DLB is predominantly associated with changes in posterior regions, such as visual association areas, and subcortical structures, and that qT1 and qT2 measurement can detect subtle changes not seen on structural volumetric imaging. Hence, quantitative MRI may compliment other imaging techniques in detecting early changes in DLB and in understanding neurobiological changes associated with the disorder.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 90%

Tissue microstructural changes in dementia with Lewy bodies revealed by quantitative MRI

Blamire

Watson

et al. 2014

J Neurol

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“…Use of this in combination with cognitive outcome will allow researchers to more accurately track the progression of mild cognitive impairment to AD. Despite the availability of blood and CSF samples from patients, some researchers insist on validating biomarkers in the aforementioned animal models (Rose et al, 2012;Spencer et al, 2013;Tai et al, 2013). Restricting biomarker research to human samples may produce viable candidates while eliminating unreliable interpretation of data that may occur when translating results from animals to humans.…”

Section: Referencesmentioning

confidence: 99%

Animal models of Alzheimer disease: historical pitfalls and a path forward

Cavanaugh

2014

ALTEX

108

109

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“…In previous work by the same authors, decreased T 1 values were found in patients with dementia with Lewy bodies compared with control subjects, highlighting the potential of T 1 measures in general to detect changes caused by neurodegeneration [21]. Using 5xFAD transgenic mice, a well-recognised AD mouse model [22–24], we have previously shown that at the age of 11 months, 5xFAD mice have reduced MRI T 1 relaxation times in the lower layers of the posterior parietal and primary somatosensory areas of the cortex and the corpus callosum compared with age-matched wild-type controls [25]. The cortex has a complex architecture that is made up of several layers, each defined by varying densities of myelin, neuronal cells, and receptors [26].…”

Section: Introductionmentioning

confidence: 99%

“…The cortex has a complex architecture that is made up of several layers, each defined by varying densities of myelin, neuronal cells, and receptors [26]. Aβ deposition also follows a layered pattern in the cortex [25, 27]; regional variations of tissue changes related to Aβ deposition, gliosis, and/or neuronal loss may not be captured in large regions of interest that include less affected areas of tissue. We previously found in the cortex of 11-month-old 5xFAD mice a pattern of T 1 reductions that broadly correspond to the pattern of Aβ reduction [25].…”

Section: Introductionmentioning

confidence: 99%

Can MRI T1 be used to detect early changes in 5xFAD Alzheimer’s mouse brain?

Spencer

Lovell

Elderfield

et al. 2016

Magn Reson Mater Phy

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ObjectivesIn the present study, we have tested whether MRI T1 relaxation time is a sensitive marker to detect early stages of amyloidosis and gliosis in the young 5xFAD transgenic mouse, a well-established animal model for Alzheimer’s disease.Materials and methods5xFAD and wild-type mice were imaged in a 4.7 T Varian horizontal bore MRI system to generate T1 quantitative maps using the spin-echo multi-slice sequence. Following immunostaining for glial fibrillary acidic protein, Iba-1, and amyloid-β, T1 and area fraction of staining were quantified in the posterior parietal and primary somatosensory cortex and corpus callosum.ResultsIn comparison with age-matched wild-type mice, we observed first signs of amyloidosis in 2.5-month-old 5xFAD mice, and development of gliosis in 5-month-old 5xFAD mice. In contrast, MRI T1 relaxation times of young, i.e., 2.5- and 5-month-old, 5xFAD mice were not significantly different to those of age-matched wild-type controls. Furthermore, although disease progression was detectable by increased amyloid-β load in the brain of 5-month-old 5xFAD mice compared with 2.5-month-old 5xFAD mice, MRI T1 relaxation time did not change.ConclusionsIn summary, our data suggest that MRI T1 relaxation time is neither a sensitive measure of disease onset nor progression at early stages in the 5xFAD mouse transgenic mouse model.

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Quantitative evaluation of MRI and histological characteristics of the 5xFAD Alzheimer mouse brain

Cited by 24 publications

References 34 publications

Tissue microstructural changes in dementia with Lewy bodies revealed by quantitative MRI

Tissue microstructural changes in dementia with Lewy bodies revealed by quantitative MRI

Animal models of Alzheimer disease: historical pitfalls and a path forward

Can MRI T1 be used to detect early changes in 5xFAD Alzheimer’s mouse brain?

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