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...

Full description

Saved in:
Bibliographic Details
Main Authors: Julia C. Colwell, Marina E. Emborg
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Aging Neuroscience
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnagi.2025.1598245/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849713155265003520
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
work_keys_str_mv AT juliaccolwell tauandtauopathiesacrossprimatespeciesimplicationsformodelingneurodegenerativedisorders
AT juliaccolwell tauandtauopathiesacrossprimatespeciesimplicationsformodelingneurodegenerativedisorders
AT marinaeemborg tauandtauopathiesacrossprimatespeciesimplicationsformodelingneurodegenerativedisorders
AT marinaeemborg tauandtauopathiesacrossprimatespeciesimplicationsformodelingneurodegenerativedisorders
AT marinaeemborg tauandtauopathiesacrossprimatespeciesimplicationsformodelingneurodegenerativedisorders