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An overview of the methodology. A, We used the APART‐QSM method to simultaneously distinguish dia‐ and paramagnetic susceptibility sources, exploring <t>Aβ</t> aggregation and brain iron levels in ex vivo human brains from individuals with AD and healthy controls. B, The imaging results were compared to the Aβ immunohistochemistry, and <t>Perls/DAB</t> <t>staining.</t> The stained slice in the figure is from AD02. The scale bar in the zoomed‐in stained sections represent 200 μm. C, Regional dia‐ and paramagnetic susceptibility values were extracted using MMP Atlas, difference between AD and HC were calculated. D, We examined the gene expression in the same brain regions using transcriptomic data obtained from the Allen Human Brain Atlas. Using PLS regression and gene ontological tools, we explored the biological processes associated with this transcriptomic profile. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; HC, healthy control; MMP, Multi‐Model Parcellation; MRI, magnetic resonance imaging; PLS, partial least squares.
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An overview of the methodology. A, We used the APART‐QSM method to simultaneously distinguish dia‐ and paramagnetic susceptibility sources, exploring <t>Aβ</t> aggregation and brain iron levels in ex vivo human brains from individuals with AD and healthy controls. B, The imaging results were compared to the Aβ immunohistochemistry, and <t>Perls/DAB</t> <t>staining.</t> The stained slice in the figure is from AD02. The scale bar in the zoomed‐in stained sections represent 200 μm. C, Regional dia‐ and paramagnetic susceptibility values were extracted using MMP Atlas, difference between AD and HC were calculated. D, We examined the gene expression in the same brain regions using transcriptomic data obtained from the Allen Human Brain Atlas. Using PLS regression and gene ontological tools, we explored the biological processes associated with this transcriptomic profile. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; HC, healthy control; MMP, Multi‐Model Parcellation; MRI, magnetic resonance imaging; PLS, partial least squares.
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An overview of the methodology. A, We used the APART‐QSM method to simultaneously distinguish dia‐ and paramagnetic susceptibility sources, exploring <t>Aβ</t> aggregation and brain iron levels in ex vivo human brains from individuals with AD and healthy controls. B, The imaging results were compared to the Aβ immunohistochemistry, and <t>Perls/DAB</t> <t>staining.</t> The stained slice in the figure is from AD02. The scale bar in the zoomed‐in stained sections represent 200 μm. C, Regional dia‐ and paramagnetic susceptibility values were extracted using MMP Atlas, difference between AD and HC were calculated. D, We examined the gene expression in the same brain regions using transcriptomic data obtained from the Allen Human Brain Atlas. Using PLS regression and gene ontological tools, we explored the biological processes associated with this transcriptomic profile. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; HC, healthy control; MMP, Multi‐Model Parcellation; MRI, magnetic resonance imaging; PLS, partial least squares.
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An overview of the methodology. A, We used the APART‐QSM method to simultaneously distinguish dia‐ and paramagnetic susceptibility sources, exploring <t>Aβ</t> aggregation and brain iron levels in ex vivo human brains from individuals with AD and healthy controls. B, The imaging results were compared to the Aβ immunohistochemistry, and <t>Perls/DAB</t> <t>staining.</t> The stained slice in the figure is from AD02. The scale bar in the zoomed‐in stained sections represent 200 μm. C, Regional dia‐ and paramagnetic susceptibility values were extracted using MMP Atlas, difference between AD and HC were calculated. D, We examined the gene expression in the same brain regions using transcriptomic data obtained from the Allen Human Brain Atlas. Using PLS regression and gene ontological tools, we explored the biological processes associated with this transcriptomic profile. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; HC, healthy control; MMP, Multi‐Model Parcellation; MRI, magnetic resonance imaging; PLS, partial least squares.
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An overview of the methodology. A, We used the APART‐QSM method to simultaneously distinguish dia‐ and paramagnetic susceptibility sources, exploring <t>Aβ</t> aggregation and brain iron levels in ex vivo human brains from individuals with AD and healthy controls. B, The imaging results were compared to the Aβ immunohistochemistry, and <t>Perls/DAB</t> <t>staining.</t> The stained slice in the figure is from AD02. The scale bar in the zoomed‐in stained sections represent 200 μm. C, Regional dia‐ and paramagnetic susceptibility values were extracted using MMP Atlas, difference between AD and HC were calculated. D, We examined the gene expression in the same brain regions using transcriptomic data obtained from the Allen Human Brain Atlas. Using PLS regression and gene ontological tools, we explored the biological processes associated with this transcriptomic profile. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; HC, healthy control; MMP, Multi‐Model Parcellation; MRI, magnetic resonance imaging; PLS, partial least squares.
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An overview of the methodology. A, We used the APART‐QSM method to simultaneously distinguish dia‐ and paramagnetic susceptibility sources, exploring Aβ aggregation and brain iron levels in ex vivo human brains from individuals with AD and healthy controls. B, The imaging results were compared to the Aβ immunohistochemistry, and Perls/DAB staining. The stained slice in the figure is from AD02. The scale bar in the zoomed‐in stained sections represent 200 μm. C, Regional dia‐ and paramagnetic susceptibility values were extracted using MMP Atlas, difference between AD and HC were calculated. D, We examined the gene expression in the same brain regions using transcriptomic data obtained from the Allen Human Brain Atlas. Using PLS regression and gene ontological tools, we explored the biological processes associated with this transcriptomic profile. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; HC, healthy control; MMP, Multi‐Model Parcellation; MRI, magnetic resonance imaging; PLS, partial least squares.

Journal: Alzheimer's & Dementia

Article Title: Distinct regional vulnerability to Aβ and iron accumulation in post mortem AD brains

doi: 10.1002/alz.14188

Figure Lengend Snippet: An overview of the methodology. A, We used the APART‐QSM method to simultaneously distinguish dia‐ and paramagnetic susceptibility sources, exploring Aβ aggregation and brain iron levels in ex vivo human brains from individuals with AD and healthy controls. B, The imaging results were compared to the Aβ immunohistochemistry, and Perls/DAB staining. The stained slice in the figure is from AD02. The scale bar in the zoomed‐in stained sections represent 200 μm. C, Regional dia‐ and paramagnetic susceptibility values were extracted using MMP Atlas, difference between AD and HC were calculated. D, We examined the gene expression in the same brain regions using transcriptomic data obtained from the Allen Human Brain Atlas. Using PLS regression and gene ontological tools, we explored the biological processes associated with this transcriptomic profile. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; HC, healthy control; MMP, Multi‐Model Parcellation; MRI, magnetic resonance imaging; PLS, partial least squares.

Article Snippet: In this study, IHC staining was performed using antibodies for Aβ (6F/3D; 1:10; Novocastra Vector Labs) and phosphorylated tau (AT8; 1:1000; Endogen), to validate the accuracy of the estimated diamagnetic susceptibility for measuring Aβ aggregation.

Techniques: Ex Vivo, Imaging, Immunohistochemistry, Staining, Gene Expression, Control, Magnetic Resonance Imaging

Correlation between regional APART‐QSM and histological measures. The linear correlation between (A) the absolute value of diamagnetic susceptibility and Aβ‐positive area (%) computed from Aβ‐IHC staining of sections, (B) the paramagnetic susceptibility and iron‐positive area (%) computed from Perls/DAB in various brain regions, including MFG, EC, HP, PHA, IPL. The AD1 samples are represented by the darker color, while the AD2 samples are represented by the lighter color. The solid line represents the linear fitting, and the dotted line represents the 95% confidence bounds. B–D, Aβ‐stained section of PHG from AD2, HP from AD2, HP from AD1. F–H, Iron‐stained section of HP from AD2, ED from AD1, PHA from AD1. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; EC, entorhinal cortex; HC, healthy control; HP, hippocampus; IHC, immunohistochemistry; IPL, inferior parietal lobe; MFG, middle frontal gyrus; PHA, para‐hippocampal gyrus.

Journal: Alzheimer's & Dementia

Article Title: Distinct regional vulnerability to Aβ and iron accumulation in post mortem AD brains

doi: 10.1002/alz.14188

Figure Lengend Snippet: Correlation between regional APART‐QSM and histological measures. The linear correlation between (A) the absolute value of diamagnetic susceptibility and Aβ‐positive area (%) computed from Aβ‐IHC staining of sections, (B) the paramagnetic susceptibility and iron‐positive area (%) computed from Perls/DAB in various brain regions, including MFG, EC, HP, PHA, IPL. The AD1 samples are represented by the darker color, while the AD2 samples are represented by the lighter color. The solid line represents the linear fitting, and the dotted line represents the 95% confidence bounds. B–D, Aβ‐stained section of PHG from AD2, HP from AD2, HP from AD1. F–H, Iron‐stained section of HP from AD2, ED from AD1, PHA from AD1. Aβ, amyloid beta; AD, Alzheimer's disease; APART‐QSM, the iterative magnetic susceptibility sources separation; DAB, diaminobenzidine; EC, entorhinal cortex; HC, healthy control; HP, hippocampus; IHC, immunohistochemistry; IPL, inferior parietal lobe; MFG, middle frontal gyrus; PHA, para‐hippocampal gyrus.

Article Snippet: In this study, IHC staining was performed using antibodies for Aβ (6F/3D; 1:10; Novocastra Vector Labs) and phosphorylated tau (AT8; 1:1000; Endogen), to validate the accuracy of the estimated diamagnetic susceptibility for measuring Aβ aggregation.

Techniques: Immunohistochemistry, Staining, Control