A 3D-induced pluripotent stem cell-derived human neural culture model to study certain molecular and biochemical aspects of Alzheimer’s disease
A 3D-induced pluripotent stem cell-derived human neural culture model to study certain molecular and biochemical aspects of Alzheimer’s disease
Purpose: Alzheimer’s disease (AD) early pathology needs better understanding and models. Here, we describe a human induced pluripotent stem cells (iPSCs)-derived 3D neural culture model to study certain aspects of AD biochemistry and pathology.
Method: iPSCs derived from controls and AD patients with Presenilin1 mutations were cultured in a 3D platform with a similar microenvironment to the brain, to differentiate into neurons and astrocytes and self-organise into 3D structures by 3 weeks of differentiation in vitro.
Results: cells express astrocytic (GFAP), neuronal (β3-Tubulin, MAP2), glutamatergic (VGLUT1), GABAergic (GAD65/67), pre-synaptic (Synapsin1) markers and a low level of neural progenitor cell (Nestin) marker after 6 and 12 weeks of differentiation in 3D. The foetal 3R Tau isoforms and adult 4R Tau isoforms were detected at 6 weeks post differentiation, showing advanced neuronal maturity. In the 3D AD cells, total and insoluble Tau levels were higher than in 3D control cells.
Conclusion: our data indicates that this model may recapitulate the early biochemical and pathological disease features and can be a relevant platform for studying early cellular and biochemical changes and the identification of drug targets.
pages447–462
Prasannan, Preeti
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Siney, Elodie Jane
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Chatterjee, Shreyasi
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Johnston, David
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Shah, Mohammad
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Mudher, Amritpal
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Willaime-Morawek, Sandrine
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14 November 2022
Prasannan, Preeti
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Siney, Elodie Jane
b72372cf-c5dd-4303-8836-57562d30953c
Chatterjee, Shreyasi
8794dd52-b2da-42cb-ac03-374fe00214d6
Johnston, David
b41163c9-b9d2-425c-af99-2a357204014e
Shah, Mohammad
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Mudher, Amritpal
ce0ccb35-ac49-4b6c-92b4-8dd5e78ac119
Willaime-Morawek, Sandrine
24a2981f-aa9e-4bf6-ad12-2ccf6b49f1c0
Prasannan, Preeti, Siney, Elodie Jane, Chatterjee, Shreyasi, Johnston, David, Shah, Mohammad, Mudher, Amritpal and Willaime-Morawek, Sandrine
(2022)
A 3D-induced pluripotent stem cell-derived human neural culture model to study certain molecular and biochemical aspects of Alzheimer’s disease.
In Vitro Models, 1, .
(doi:10.1007/s44164-022-00038-5).
Abstract
Purpose: Alzheimer’s disease (AD) early pathology needs better understanding and models. Here, we describe a human induced pluripotent stem cells (iPSCs)-derived 3D neural culture model to study certain aspects of AD biochemistry and pathology.
Method: iPSCs derived from controls and AD patients with Presenilin1 mutations were cultured in a 3D platform with a similar microenvironment to the brain, to differentiate into neurons and astrocytes and self-organise into 3D structures by 3 weeks of differentiation in vitro.
Results: cells express astrocytic (GFAP), neuronal (β3-Tubulin, MAP2), glutamatergic (VGLUT1), GABAergic (GAD65/67), pre-synaptic (Synapsin1) markers and a low level of neural progenitor cell (Nestin) marker after 6 and 12 weeks of differentiation in 3D. The foetal 3R Tau isoforms and adult 4R Tau isoforms were detected at 6 weeks post differentiation, showing advanced neuronal maturity. In the 3D AD cells, total and insoluble Tau levels were higher than in 3D control cells.
Conclusion: our data indicates that this model may recapitulate the early biochemical and pathological disease features and can be a relevant platform for studying early cellular and biochemical changes and the identification of drug targets.
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s44164-022-00038-5
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Accepted/In Press date: 20 October 2022
Published date: 14 November 2022
Identifiers
Local EPrints ID: 472690
URI: http://eprints.soton.ac.uk/id/eprint/472690
ISSN: 2731-3441
PURE UUID: 2e123c4a-6211-4148-9dc3-b1be0635906a
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Date deposited: 14 Dec 2022 17:45
Last modified: 19 Mar 2024 02:41
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Author:
Preeti Prasannan
Author:
Elodie Jane Siney
Author:
Shreyasi Chatterjee
Author:
David Johnston
Author:
Mohammad Shah
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