Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities
Abstract Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07499-w |
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| author | Filippa Lo Cascio Suhyeorn Park Urmi Sengupta Nicha Puangmalai Nemil Bhatt Nikita Shchankin Cynthia Jerez Naomi Moreno Alice Bittar Rhea Xavier Yingxin Zhao Cankun Wang Hongjun Fu Qin Ma Mauro Montalbano Rakez Kayed |
| author_facet | Filippa Lo Cascio Suhyeorn Park Urmi Sengupta Nicha Puangmalai Nemil Bhatt Nikita Shchankin Cynthia Jerez Naomi Moreno Alice Bittar Rhea Xavier Yingxin Zhao Cankun Wang Hongjun Fu Qin Ma Mauro Montalbano Rakez Kayed |
| author_sort | Filippa Lo Cascio |
| collection | DOAJ |
| description | Abstract Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs. Here, we investigate the structural and functional differences of amplified brain-derived tau oligomers (aBDTOs) from AD, DLB, and PSP. Our results indicate that the aBDTOs possess different structural and morphological features that impact neuronal function, gene regulation, and ultimately disease progression. The distinct tau oligomeric polymorphs may thus contribute to the development of clinical phenotypes and shape the progression of diseases. Our results can provide insight into developing personalized therapy to target a specific neurotoxic tau polymorph. |
| format | Article |
| id | doaj-art-c938ae1cbd5145398e4d33a24b81635d |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-c938ae1cbd5145398e4d33a24b81635d2025-01-19T12:35:42ZengNature PortfolioCommunications Biology2399-36422025-01-018111810.1038/s42003-025-07499-wBrain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activitiesFilippa Lo Cascio0Suhyeorn Park1Urmi Sengupta2Nicha Puangmalai3Nemil Bhatt4Nikita Shchankin5Cynthia Jerez6Naomi Moreno7Alice Bittar8Rhea Xavier9Yingxin Zhao10Cankun Wang11Hongjun Fu12Qin Ma13Mauro Montalbano14Rakez Kayed15Mitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchSealy Center for Molecular Medicine, University of Texas Medical BranchDepartment of Biomedical Informatics, The Ohio State UniversityDepartment of Neuroscience, The Ohio State UniversityDepartment of Biomedical Informatics, The Ohio State UniversityMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchMitchell Center for Neurodegenerative Diseases, University of Texas Medical BranchAbstract Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs. Here, we investigate the structural and functional differences of amplified brain-derived tau oligomers (aBDTOs) from AD, DLB, and PSP. Our results indicate that the aBDTOs possess different structural and morphological features that impact neuronal function, gene regulation, and ultimately disease progression. The distinct tau oligomeric polymorphs may thus contribute to the development of clinical phenotypes and shape the progression of diseases. Our results can provide insight into developing personalized therapy to target a specific neurotoxic tau polymorph.https://doi.org/10.1038/s42003-025-07499-w |
| spellingShingle | Filippa Lo Cascio Suhyeorn Park Urmi Sengupta Nicha Puangmalai Nemil Bhatt Nikita Shchankin Cynthia Jerez Naomi Moreno Alice Bittar Rhea Xavier Yingxin Zhao Cankun Wang Hongjun Fu Qin Ma Mauro Montalbano Rakez Kayed Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities Communications Biology |
| title | Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities |
| title_full | Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities |
| title_fullStr | Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities |
| title_full_unstemmed | Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities |
| title_short | Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities |
| title_sort | brain derived tau oligomer polymorphs distinct aggregations stability profiles and biological activities |
| url | https://doi.org/10.1038/s42003-025-07499-w |
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