The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes
We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Ab peptide seque...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal Article |
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Public Library of Science
2013
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| Online Access: | http://hdl.handle.net/20.500.11937/10783 |
| _version_ | 1848747627766611968 |
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| author | Sharman, Matthew Moussavi Nik, Seyyed Chen, Mengqi Ong, Daniel Wijaya, Linda Laws, Simon Taddei, Kevin Newman, Morgan Lardelli, Michael Martins, Ralph Verdile, Giuseppe |
| author_facet | Sharman, Matthew Moussavi Nik, Seyyed Chen, Mengqi Ong, Daniel Wijaya, Linda Laws, Simon Taddei, Kevin Newman, Morgan Lardelli, Michael Martins, Ralph Verdile, Giuseppe |
| author_sort | Sharman, Matthew |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Ab peptide sequence identical to human Ab. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1(b-secretase) transcription and down-regulation of ADAM10 (a-secretase) transcription which should increase release of Ab from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases c-secretase activity and Ab synthesis, is not uniquely human or aberrant as previously believed. We show thatPS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Ab concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes |
| first_indexed | 2025-11-14T06:52:10Z |
| format | Journal Article |
| id | curtin-20.500.11937-10783 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:52:10Z |
| publishDate | 2013 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-107832017-09-13T14:55:05Z The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes Sharman, Matthew Moussavi Nik, Seyyed Chen, Mengqi Ong, Daniel Wijaya, Linda Laws, Simon Taddei, Kevin Newman, Morgan Lardelli, Michael Martins, Ralph Verdile, Giuseppe AD-Related Genes Cholesterol Intake Alzheimer’s Disease We investigated the guinea pig, Cavia porcellus, as a model for Alzheimer’s disease (AD), both in terms of the conservation of genes involved in AD and the regulatory responses of these to a known AD risk factor - high cholesterol intake. Unlike rats and mice, guinea pigs possess an Ab peptide sequence identical to human Ab. Consistent with the commonality between cardiovascular and AD risk factors in humans, we saw that a high cholesterol diet leads to up-regulation of BACE1(b-secretase) transcription and down-regulation of ADAM10 (a-secretase) transcription which should increase release of Ab from APP. Significantly, guinea pigs possess isoforms of AD-related genes found in humans but not present in mice or rats. For example, we discovered that the truncated PS2V isoform of human PSEN2, that is found at raised levels in AD brains and that increases c-secretase activity and Ab synthesis, is not uniquely human or aberrant as previously believed. We show thatPS2V formation is up-regulated by hypoxia and a high-cholesterol diet while, consistent with observations in humans, Ab concentrations are raised in some brain regions but not others. Also like humans, but unlike mice, the guinea pig gene encoding tau, MAPT, encodes isoforms with both three and four microtubule binding domains, and cholesterol alters the ratio of these isoforms. We conclude that AD-related genes are highly conserved and more similar to human than the rat or mouse. Guinea pigs represent a superior rodent model for analysis of the impact of dietary factors such as cholesterol on the regulation of AD-related genes 2013 Journal Article http://hdl.handle.net/20.500.11937/10783 10.1371/journal.pone.0066235 Public Library of Science unknown |
| spellingShingle | AD-Related Genes Cholesterol Intake Alzheimer’s Disease Sharman, Matthew Moussavi Nik, Seyyed Chen, Mengqi Ong, Daniel Wijaya, Linda Laws, Simon Taddei, Kevin Newman, Morgan Lardelli, Michael Martins, Ralph Verdile, Giuseppe The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes |
| title | The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes |
| title_full | The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes |
| title_fullStr | The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes |
| title_full_unstemmed | The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes |
| title_short | The Guinea Pig as a Model for Sporadic Alzheimer’s Disease (AD): The Impact of Cholesterol Intake on Expression of AD-Related Genes |
| title_sort | guinea pig as a model for sporadic alzheimer’s disease (ad): the impact of cholesterol intake on expression of ad-related genes |
| topic | AD-Related Genes Cholesterol Intake Alzheimer’s Disease |
| url | http://hdl.handle.net/20.500.11937/10783 |