Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease
The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Nature Research
2024
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| _version_ | 1824458757987368960 |
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| author | Fowler, SL Behr, TS Turkes, E O’Brien, DP Cauhy, PM Rawlinson, I Edmonds, M Foiani, MS Schaler, A Crowley, G Bez, S Ficulle, E Tsefou, E Fischer, R Geary, B Gaur, P Miller, C D’Acunzo, P Levy, E Duff, KE Ryskeldi-Falcon, B |
| author_facet | Fowler, SL Behr, TS Turkes, E O’Brien, DP Cauhy, PM Rawlinson, I Edmonds, M Foiani, MS Schaler, A Crowley, G Bez, S Ficulle, E Tsefou, E Fischer, R Geary, B Gaur, P Miller, C D’Acunzo, P Levy, E Duff, KE Ryskeldi-Falcon, B |
| author_sort | Fowler, SL |
| collection | OXFORD |
| description | The abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from individuals with AD. We found tau filaments composed mainly of truncated tau that were enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD. |
| first_indexed | 2025-02-19T04:30:58Z |
| format | Journal article |
| id | oxford-uuid:07a8d3a5-979f-4242-b466-07fd37de7c6a |
| institution | University of Oxford |
| language | English |
| last_indexed | 2025-02-19T04:30:58Z |
| publishDate | 2024 |
| publisher | Nature Research |
| record_format | dspace |
| spelling | oxford-uuid:07a8d3a5-979f-4242-b466-07fd37de7c6a2025-01-09T20:15:15ZTau filaments are tethered within brain extracellular vesicles in Alzheimer’s diseaseJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:07a8d3a5-979f-4242-b466-07fd37de7c6aEnglishJisc Publications RouterNature Research2024Fowler, SLBehr, TSTurkes, EO’Brien, DPCauhy, PMRawlinson, IEdmonds, MFoiani, MSSchaler, ACrowley, GBez, SFiculle, ETsefou, EFischer, RGeary, BGaur, PMiller, CD’Acunzo, PLevy, EDuff, KERyskeldi-Falcon, BThe abnormal assembly of tau protein in neurons is a pathological hallmark of multiple neurodegenerative diseases, including Alzheimer’s disease (AD). Assembled tau associates with extracellular vesicles (EVs) in the central nervous system of individuals with AD, which is linked to its clearance and prion-like propagation. However, the identities of the assembled tau species and EVs, as well as how they associate, are not known. Here, we combined quantitative mass spectrometry, cryo-electron tomography and single-particle cryo-electron microscopy to study brain EVs from individuals with AD. We found tau filaments composed mainly of truncated tau that were enclosed within EVs enriched in endo-lysosomal proteins. We observed multiple filament interactions, including with molecules that tethered filaments to the EV limiting membrane, suggesting selective packaging. Our findings will guide studies into the molecular mechanisms of EV-mediated secretion of assembled tau and inform the targeting of EV-associated tau as potential therapeutic and biomarker strategies for AD. |
| spellingShingle | Fowler, SL Behr, TS Turkes, E O’Brien, DP Cauhy, PM Rawlinson, I Edmonds, M Foiani, MS Schaler, A Crowley, G Bez, S Ficulle, E Tsefou, E Fischer, R Geary, B Gaur, P Miller, C D’Acunzo, P Levy, E Duff, KE Ryskeldi-Falcon, B Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease |
| title | Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease |
| title_full | Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease |
| title_fullStr | Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease |
| title_full_unstemmed | Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease |
| title_short | Tau filaments are tethered within brain extracellular vesicles in Alzheimer’s disease |
| title_sort | tau filaments are tethered within brain extracellular vesicles in alzheimer s disease |
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