Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation.
Amyloid β (Aβ) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of Aβ-induced impairment o...
| Main Authors: | , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2011
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| _version_ | 1797058627819798528 |
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| author | Shipton, O Leitz, JR Dworzak, J Acton, C Tunbridge, E Denk, F Dawson, H Vitek, M Wade-Martins, R Paulsen, O Vargas-Caballero, M |
| author_facet | Shipton, O Leitz, JR Dworzak, J Acton, C Tunbridge, E Denk, F Dawson, H Vitek, M Wade-Martins, R Paulsen, O Vargas-Caballero, M |
| author_sort | Shipton, O |
| collection | OXFORD |
| description | Amyloid β (Aβ) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of Aβ-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knock-out of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents Aβ-induced impairment of LTP. Moreover, we show that Aβ increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by Aβ and prevents Aβ-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for Aβ to impair synaptic plasticity in the hippocampus and suggest that the Aβ-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between Aβ and tau could be a promising strategy for treating cognitive impairment in MCI and early AD. |
| first_indexed | 2024-03-06T19:53:00Z |
| format | Journal article |
| id | oxford-uuid:249815df-d056-4e57-9d04-a61b3e83e17a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T19:53:00Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:249815df-d056-4e57-9d04-a61b3e83e17a2022-03-26T11:50:58ZTau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:249815df-d056-4e57-9d04-a61b3e83e17aEnglishSymplectic Elements at Oxford2011Shipton, OLeitz, JRDworzak, JActon, CTunbridge, EDenk, FDawson, HVitek, MWade-Martins, RPaulsen, OVargas-Caballero, MAmyloid β (Aβ) and tau protein are both implicated in memory impairment, mild cognitive impairment (MCI), and early Alzheimer's disease (AD), but whether and how they interact is unknown. Consequently, we asked whether tau protein is required for the robust phenomenon of Aβ-induced impairment of hippocampal long-term potentiation (LTP), a widely accepted cellular model of memory. We used wild-type mice and mice with a genetic knock-out of tau protein and recorded field potentials in an acute slice preparation. We demonstrate that the absence of tau protein prevents Aβ-induced impairment of LTP. Moreover, we show that Aβ increases tau phosphorylation and that a specific inhibitor of the tau kinase glycogen synthase kinase 3 blocks the increased tau phosphorylation induced by Aβ and prevents Aβ-induced impairment of LTP in wild-type mice. Together, these findings show that tau protein is required for Aβ to impair synaptic plasticity in the hippocampus and suggest that the Aβ-induced impairment of LTP is mediated by tau phosphorylation. We conclude that preventing the interaction between Aβ and tau could be a promising strategy for treating cognitive impairment in MCI and early AD. |
| spellingShingle | Shipton, O Leitz, JR Dworzak, J Acton, C Tunbridge, E Denk, F Dawson, H Vitek, M Wade-Martins, R Paulsen, O Vargas-Caballero, M Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. |
| title | Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. |
| title_full | Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. |
| title_fullStr | Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. |
| title_full_unstemmed | Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. |
| title_short | Tau protein is required for amyloid {beta}-induced impairment of hippocampal long-term potentiation. |
| title_sort | tau protein is required for amyloid beta induced impairment of hippocampal long term potentiation |
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