Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders
Tauopathies are neurodegenerative disorders characterized by the abnormal accumulation and aggregation of hyperphosphorylated tau protein. They can be primary or secondary depending on whether tau inclusions are the predominant pathology (e.g.: frontotemporal dementia related to tau) or are found wi...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1598245/full |
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| author | Julia C. Colwell Julia C. Colwell Marina E. Emborg Marina E. Emborg Marina E. Emborg |
| author_facet | Julia C. Colwell Julia C. Colwell Marina E. Emborg Marina E. Emborg Marina E. Emborg |
| author_sort | Julia C. Colwell |
| collection | DOAJ |
| description | Tauopathies are neurodegenerative disorders characterized by the abnormal accumulation and aggregation of hyperphosphorylated tau protein. They can be primary or secondary depending on whether tau inclusions are the predominant pathology (e.g.: frontotemporal dementia related to tau) or are found with other proteinopathies (e.g.: Alzheimer’s disease), respectively. Currently, there are no effective treatments to prevent or slow down progressive tau accumulation. Animal models play a critical role in the efforts to unravel the mechanisms leading to tauopathies and identifying therapeutic targets. Nonhuman primates (NHPs) present several advantages for the study of tauopathies, as they have complex neuroanatomy and behavior that resembles human traits, and their tau gene and protein are highly conserved. Moreover, aged NHPs, like humans, can present various tau inclusions in their brains, although whether NHPs can develop human-like tau-related neurodegenerative disorders is currently debated. The main goal of this review is to analyze available reports on tau pathologies and models of tauopathies in NHPs considering the complexity of the tau protein and associated tau pathologies. Here, we first summarize current available information on human and NHP tau under physiological conditions in order to highlight species differences and gaps in knowledge. We then analyze reports on tau pathologies in aged NHPs compared to human aging and tauopathy, followed by an evaluation of current and emerging NHP models of tauopathy. Lastly, we discuss the practical and ethical challenges of doing tauopathy research in NHPs, and how to best leverage it to ultimately find solutions for patients with these disorders. |
| format | Article |
| id | doaj-art-74cc95aa35564a81a63d8feebb01949b |
| institution | DOAJ |
| issn | 1663-4365 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj-art-74cc95aa35564a81a63d8feebb01949b2025-08-20T03:14:02ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652025-07-011710.3389/fnagi.2025.15982451598245Tau and tauopathies across primate species: implications for modeling neurodegenerative disordersJulia C. Colwell0Julia C. Colwell1Marina E. Emborg2Marina E. Emborg3Marina E. Emborg4Preclinical Parkinson’s Research Program, Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, United StatesCellular and Molecular Pathology Graduate Program, University of Wisconsin, Madison, WI, United StatesPreclinical Parkinson’s Research Program, Wisconsin National Primate Research Center, University of Wisconsin, Madison, WI, United StatesCellular and Molecular Pathology Graduate Program, University of Wisconsin, Madison, WI, United StatesDepartment of Medical Physics, University of Wisconsin, Madison, WI, United StatesTauopathies are neurodegenerative disorders characterized by the abnormal accumulation and aggregation of hyperphosphorylated tau protein. They can be primary or secondary depending on whether tau inclusions are the predominant pathology (e.g.: frontotemporal dementia related to tau) or are found with other proteinopathies (e.g.: Alzheimer’s disease), respectively. Currently, there are no effective treatments to prevent or slow down progressive tau accumulation. Animal models play a critical role in the efforts to unravel the mechanisms leading to tauopathies and identifying therapeutic targets. Nonhuman primates (NHPs) present several advantages for the study of tauopathies, as they have complex neuroanatomy and behavior that resembles human traits, and their tau gene and protein are highly conserved. Moreover, aged NHPs, like humans, can present various tau inclusions in their brains, although whether NHPs can develop human-like tau-related neurodegenerative disorders is currently debated. The main goal of this review is to analyze available reports on tau pathologies and models of tauopathies in NHPs considering the complexity of the tau protein and associated tau pathologies. Here, we first summarize current available information on human and NHP tau under physiological conditions in order to highlight species differences and gaps in knowledge. We then analyze reports on tau pathologies in aged NHPs compared to human aging and tauopathy, followed by an evaluation of current and emerging NHP models of tauopathy. Lastly, we discuss the practical and ethical challenges of doing tauopathy research in NHPs, and how to best leverage it to ultimately find solutions for patients with these disorders.https://www.frontiersin.org/articles/10.3389/fnagi.2025.1598245/fulltautauopathiesnonhuman primatesAlzheimer’s diseasefrontemporal dementianeurofibrillary tangles |
| spellingShingle | Julia C. Colwell Julia C. Colwell Marina E. Emborg Marina E. Emborg Marina E. Emborg Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders Frontiers in Aging Neuroscience tau tauopathies nonhuman primates Alzheimer’s disease frontemporal dementia neurofibrillary tangles |
| title | Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders |
| title_full | Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders |
| title_fullStr | Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders |
| title_full_unstemmed | Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders |
| title_short | Tau and tauopathies across primate species: implications for modeling neurodegenerative disorders |
| title_sort | tau and tauopathies across primate species implications for modeling neurodegenerative disorders |
| topic | tau tauopathies nonhuman primates Alzheimer’s disease frontemporal dementia neurofibrillary tangles |
| url | https://www.frontiersin.org/articles/10.3389/fnagi.2025.1598245/full |
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