Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model.
Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-ß (Aß) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the inte...
| Main Authors: | , , , , , , |
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| Format: | Journal Article |
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Federation of American Societies for Experimental Biology
2017
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| Online Access: | http://hdl.handle.net/20.500.11937/56653 |
| _version_ | 1848759905716011008 |
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| author | Wijesekara, N. Ahrens, R. Sabale, M. Wu, L. Ha, K. Verdile, Giuseppe Fraser, P. |
| author_facet | Wijesekara, N. Ahrens, R. Sabale, M. Wu, L. Ha, K. Verdile, Giuseppe Fraser, P. |
| author_sort | Wijesekara, N. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-ß (Aß) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance. Aß and IAPP amyloid co-deposition increased tau phosphorylation, and a reduction in pancreatic ß-cell mass was detected in islets. Increased brain Aß deposition and tau phosphorylation and reduced insulin levels and signaling were accompanied by extensive synaptic loss and decreased neuronal counts. Aß immunization rescued the peripheral insulin resistance and hyperglycemia, suggesting a role for Aß in T2D pathogenesis for individuals predisposed to AD. These findings demonstrate that Aß and IAPP are key factors in the overlapping pathologies of AD and T2D.-Wijesekara, N., Ahrens, R., Sabale, M., Wu, L., Ha, K., Verdile, G., Fraser, P. E. Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. |
| first_indexed | 2025-11-14T10:07:19Z |
| format | Journal Article |
| id | curtin-20.500.11937-56653 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T10:07:19Z |
| publishDate | 2017 |
| publisher | Federation of American Societies for Experimental Biology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-566532018-02-12T03:45:17Z Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. Wijesekara, N. Ahrens, R. Sabale, M. Wu, L. Ha, K. Verdile, Giuseppe Fraser, P. Alzheimer's disease (AD) and type 2 diabetes (T2D) present a significant risk to each other. AD and T2D are characterized by deposition of cerebral amyloid-ß (Aß) and pancreatic human islet amyloid polypeptide (hIAPP), respectively. We investigated the role of amyloidogenic proteins in the interplay between these diseases. A novel double transgenic mouse model combining T2D and AD was generated and characterized. AD-related amyloid transgenic mice coexpressing hIAPP displayed peripheral insulin resistance, hyperglycemia, and glucose intolerance. Aß and IAPP amyloid co-deposition increased tau phosphorylation, and a reduction in pancreatic ß-cell mass was detected in islets. Increased brain Aß deposition and tau phosphorylation and reduced insulin levels and signaling were accompanied by extensive synaptic loss and decreased neuronal counts. Aß immunization rescued the peripheral insulin resistance and hyperglycemia, suggesting a role for Aß in T2D pathogenesis for individuals predisposed to AD. These findings demonstrate that Aß and IAPP are key factors in the overlapping pathologies of AD and T2D.-Wijesekara, N., Ahrens, R., Sabale, M., Wu, L., Ha, K., Verdile, G., Fraser, P. E. Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. 2017 Journal Article http://hdl.handle.net/20.500.11937/56653 10.1096/fj.201700431R Federation of American Societies for Experimental Biology unknown |
| spellingShingle | Wijesekara, N. Ahrens, R. Sabale, M. Wu, L. Ha, K. Verdile, Giuseppe Fraser, P. Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. |
| title | Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. |
| title_full | Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. |
| title_fullStr | Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. |
| title_full_unstemmed | Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. |
| title_short | Amyloid-ß and islet amyloid pathologies link Alzheimer disease and type 2 diabetes in a transgenic model. |
| title_sort | amyloid-ß and islet amyloid pathologies link alzheimer disease and type 2 diabetes in a transgenic model. |
| url | http://hdl.handle.net/20.500.11937/56653 |