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Contributions of a high-fat diet to Alzheimer's disease-related decline: A longitudinal behavioural and structural neuroimaging study in mouse models.

NeuroImage. Clinical | 2019

Obesity is recognized as a significant risk factor for Alzheimer's disease (AD). Studies have supported that obesity accelerates AD-related pathophysiology and memory impairment in mouse models of AD. However, the nature of the brain structure-behaviour relationship mediating this acceleration remains unclear. In this manuscript we evaluated the impact of adolescent obesity on the brain morphology of the triple transgenic mouse model of AD (3xTg) and a non-transgenic control model of the same background strain (B6129s) using longitudinally acquired structural magnetic resonance imaging (MRI). At 8 weeks of age, animals were placed on a high-fat diet (HFD) or an ingredient-equivalent control diet (CD). Structural images were acquired at 8, 16, and 24 weeks. At 25 weeks, animals underwent the novel object recognition (NOR) task and the Morris water maze (MWM) to assess short-term non-associative memory and spatial memory, respectively. All analyses were carried out across four groups: B6129s-CD and -HFD and 3xTg-CD and -HFD. Neuroanatomical changes in MRI-derived brain morphology were assessed using volumetric and deformation-based analyses. HFD-induced obesity during adolescence exacerbated brain volume alterations by adult life in the 3xTg mouse model in comparison to control-fed mice and mediated volumetric alterations of select brain regions, such as the hippocampus. Further, HFD-induced obesity aggravated memory in all mice, lowering certain memory measures of B6129s control mice to the level of 3xTg mice maintained on a CD. Moreover, decline in the volumetric trajectories of hippocampal regions for all mice were associated with the degree of spatial memory impairments on the MWM. Our results suggest that obesity may interact with the brain changes associated with AD-related pathology in the 3xTg mouse model to aggravate brain atrophy and memory impairments and similarly impair brain structural integrity and memory capacity of non-transgenic mice. Further insight into this process may have significant implications in the development of lifestyle interventions for treatment of AD.

Pubmed ID: 30503215 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


MINC (tool)

RRID:SCR_002391

A medical imaging data format and an associated set of tools and libraries including a 3 level API for medical image analysis with a particular focus on the needs of research. There are also a number of tools including Registration and Non-Uniformity correction.

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ggplot2 (tool)

RRID:SCR_014601

Open source software package for statistical programming language R to create plots based on grammar of graphics. Used for data visualization to break up graphs into semantic components such as scales and layers.

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129S1/SvImJ (tool)

RRID:IMSR_JAX:002448

Mus musculus with name 129S1/SvImJ from IMSR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax (organism)

RRID:MMRRC_034830-JAX

Mus musculus with name B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax from MMRRC.

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B6129SF2/J (organism)

RRID:IMSR_JAX:101045

Mus musculus with name B6129SF2/J from IMSR.

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RStudio (software resource)

RRID:SCR_000432

Open source and enterprise ready professional software for R statistical computing environment. Integrated development environment for R. Includes console, syntax highlighting editor that supports direct code execution, as well as tools for plotting, history, debugging and workspace management. Available in open source and commercial editions and runs on desktop Windows, Mac, and Linux or in browser connected to RStudio Server or RStudio Server Pro (Debian/Ubuntu, RedHat/CentOS, and SUSE Linux).

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minc-toolkit (software resource)

RRID:SCR_014138

A set of MINC-based image processing tools packaged together. It includes MINC, N3, BICPL, EBKTS, ANIMAL, INSECT, BEaST, Register, Display, and xdisp.

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B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax (organism)

RRID:MMRRC_034830-JAX

Mus musculus with name B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax from MMRRC.

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minc-toolkit (software resource)

RRID:SCR_014138

A set of MINC-based image processing tools packaged together. It includes MINC, N3, BICPL, EBKTS, ANIMAL, INSECT, BEaST, Register, Display, and xdisp.

View all literature mentions

B6129SF2/J (organism)

RRID:IMSR_JAX:101045

Mus musculus with name B6129SF2/J from IMSR.

View all literature mentions

RStudio (software resource)

RRID:SCR_000432

Open source and enterprise ready professional software for R statistical computing environment. Integrated development environment for R. Includes console, syntax highlighting editor that supports direct code execution, as well as tools for plotting, history, debugging and workspace management. Available in open source and commercial editions and runs on desktop Windows, Mac, and Linux or in browser connected to RStudio Server or RStudio Server Pro (Debian/Ubuntu, RedHat/CentOS, and SUSE Linux).

View all literature mentions

B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax (organism)

RRID:MMRRC_034830-JAX

Mus musculus with name B6;129-Tg(APPSwe,tauP301L)1Lfa Psen1tm1Mpm/Mmjax from MMRRC.

View all literature mentions

B6129SF2/J (organism)

RRID:IMSR_JAX:101045

Mus musculus with name B6129SF2/J from IMSR.

View all literature mentions

minc-toolkit (software resource)

RRID:SCR_014138

A set of MINC-based image processing tools packaged together. It includes MINC, N3, BICPL, EBKTS, ANIMAL, INSECT, BEaST, Register, Display, and xdisp.

View all literature mentions

RStudio (software resource)

RRID:SCR_000432

Open source and enterprise ready professional software for R statistical computing environment. Integrated development environment for R. Includes console, syntax highlighting editor that supports direct code execution, as well as tools for plotting, history, debugging and workspace management. Available in open source and commercial editions and runs on desktop Windows, Mac, and Linux or in browser connected to RStudio Server or RStudio Server Pro (Debian/Ubuntu, RedHat/CentOS, and SUSE Linux).

View all literature mentions