Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease.
Numerous studies of the human brain supported by experimental results from rodent and cell models point to a central role for intracellular amyloid beta (Aβ) in the onset of Alzheimer's disease (AD). In a rat model used to study AD, it was recently shown that in layer II neurons of the anteriol...
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Public Library of Science (PLoS)
2025-01-01
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| Series: | PLoS Computational Biology |
| Online Access: | https://doi.org/10.1371/journal.pcbi.1012709 |
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| author | Asgeir Kobro-Flatmoen Stig W Omholt |
| author_facet | Asgeir Kobro-Flatmoen Stig W Omholt |
| author_sort | Asgeir Kobro-Flatmoen |
| collection | DOAJ |
| description | Numerous studies of the human brain supported by experimental results from rodent and cell models point to a central role for intracellular amyloid beta (Aβ) in the onset of Alzheimer's disease (AD). In a rat model used to study AD, it was recently shown that in layer II neurons of the anteriolateral entorhinal cortex expressing high levels of the glycoprotein reelin (Re+alECLII neurons), reelin and Aβ engage in a direct protein-protein interaction. If reelin functions as a sink for intracellular Aβ and if the binding to reelin makes Aβ physiologically inert, it implies that reelin can prevent the neuron from being exposed to the harmful effects typically associated with increased levels of oligomeric Aβ. Considering that reelin expression is extraordinarily high in Re+alECLII neurons compared to most other cortical neurons, such a protective role appears to be very difficult to reconcile with the fact that this subset of ECLII neurons is clearly a major cradle for the onset of AD. Here, we show that this conundrum can be resolved if Re+alECLII neurons have a higher maximum production capacity of Aβ than neurons expressing low levels of reelin, and we provide a rationale for why this difference has evolved. |
| format | Article |
| id | doaj-art-a85ba3b37da744d7968cbbff8dcf9e52 |
| institution | Kabale University |
| issn | 1553-734X 1553-7358 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Computational Biology |
| spelling | doaj-art-a85ba3b37da744d7968cbbff8dcf9e522025-02-05T05:30:39ZengPublic Library of Science (PLoS)PLoS Computational Biology1553-734X1553-73582025-01-01211e101270910.1371/journal.pcbi.1012709Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease.Asgeir Kobro-FlatmoenStig W OmholtNumerous studies of the human brain supported by experimental results from rodent and cell models point to a central role for intracellular amyloid beta (Aβ) in the onset of Alzheimer's disease (AD). In a rat model used to study AD, it was recently shown that in layer II neurons of the anteriolateral entorhinal cortex expressing high levels of the glycoprotein reelin (Re+alECLII neurons), reelin and Aβ engage in a direct protein-protein interaction. If reelin functions as a sink for intracellular Aβ and if the binding to reelin makes Aβ physiologically inert, it implies that reelin can prevent the neuron from being exposed to the harmful effects typically associated with increased levels of oligomeric Aβ. Considering that reelin expression is extraordinarily high in Re+alECLII neurons compared to most other cortical neurons, such a protective role appears to be very difficult to reconcile with the fact that this subset of ECLII neurons is clearly a major cradle for the onset of AD. Here, we show that this conundrum can be resolved if Re+alECLII neurons have a higher maximum production capacity of Aβ than neurons expressing low levels of reelin, and we provide a rationale for why this difference has evolved.https://doi.org/10.1371/journal.pcbi.1012709 |
| spellingShingle | Asgeir Kobro-Flatmoen Stig W Omholt Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease. PLoS Computational Biology |
| title | Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease. |
| title_full | Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease. |
| title_fullStr | Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease. |
| title_full_unstemmed | Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease. |
| title_short | Intraneuronal binding of amyloid beta with reelin-Implications for the onset of Alzheimer's disease. |
| title_sort | intraneuronal binding of amyloid beta with reelin implications for the onset of alzheimer s disease |
| url | https://doi.org/10.1371/journal.pcbi.1012709 |
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