Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy
Alzheimer’s disease (AD), the most common tauopathy, is an age-dependent, progressive neurodegenerative disease. Epidemiological studies implicate the role of genetic background in the onset and progression of AD. Despite mutations in familial AD, several risk factors have been implicated in sporadi...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-12-01
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| Series: | Frontiers in Aging Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnagi.2019.00343/full |
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| author | Tomas Smolek Tomas Smolek Veronika Cubinkova Veronika Cubinkova Veronika Brezovakova Bernadeta Valachova Peter Szalay Peter Szalay Norbert Zilka Norbert Zilka Santosh Jadhav Santosh Jadhav |
| author_facet | Tomas Smolek Tomas Smolek Veronika Cubinkova Veronika Cubinkova Veronika Brezovakova Bernadeta Valachova Peter Szalay Peter Szalay Norbert Zilka Norbert Zilka Santosh Jadhav Santosh Jadhav |
| author_sort | Tomas Smolek |
| collection | DOAJ |
| description | Alzheimer’s disease (AD), the most common tauopathy, is an age-dependent, progressive neurodegenerative disease. Epidemiological studies implicate the role of genetic background in the onset and progression of AD. Despite mutations in familial AD, several risk factors have been implicated in sporadic AD, of which the onset is unknown. In AD, there is a sequential and hierarchical spread of tau pathology to other brain areas. Studies have strived to understand the factors that influence this characteristic spread. Using transgenic rat models with different genetic backgrounds, we reported that the genetic background may influence the manifestation of neurofibrillary pathology. In this study we investigated whether genetic background has an influence in the spread of tau pathology, using hippocampal inoculations of insoluble tau from AD brains in rodent models of tauopathy with either a spontaneously hypertensive (SHR72) or Wistar-Kyoto (WKY72) genetic background. We observed that insoluble tau from human AD induced AT8-positive neurofibrillary structures in the hippocampus of both lines. However, there was no significant difference in the amount of neurofibrillary structures, but the extent of spread was prominent in the W72 line. On the other hand, we observed significantly higher levels of AT8-positive structures in the parietal and frontal cortical areas in W72 when compared to SHR72. Interestingly, we also observed that the microglia in these brain areas in W72 were predominantly phagocytic in morphology (62.4% in parietal and 47.3% in frontal), while in SHR72 the microglia were either reactive or ramified (67.2% in parietal and 84.7% in frontal). The microglia in the hippocampus and occipital cortex in both lines were reactive or ramified structures. Factors such as gender or age are not responsible for the differences observed in these animals. Put together, our results, for the first time, show that the immune response modulating genetic variability is one of the factors that influences the propagation of tau neurofibrillary pathology. |
| first_indexed | 2024-12-22T07:43:01Z |
| format | Article |
| id | doaj.art-b20010c9f4f44b43a9000c599811f726 |
| institution | Directory Open Access Journal |
| issn | 1663-4365 |
| language | English |
| last_indexed | 2024-12-22T07:43:01Z |
| publishDate | 2019-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Aging Neuroscience |
| spelling | doaj.art-b20010c9f4f44b43a9000c599811f7262022-12-21T18:33:42ZengFrontiers Media S.A.Frontiers in Aging Neuroscience1663-43652019-12-011110.3389/fnagi.2019.00343495590Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of TauopathyTomas Smolek0Tomas Smolek1Veronika Cubinkova2Veronika Cubinkova3Veronika Brezovakova4Bernadeta Valachova5Peter Szalay6Peter Szalay7Norbert Zilka8Norbert Zilka9Santosh Jadhav10Santosh Jadhav11Institute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaAxon Neuroscience R&D Services SE, Bratislava, SlovakiaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaAxon Neuroscience R&D Services SE, Bratislava, SlovakiaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaAxon Neuroscience R&D Services SE, Bratislava, SlovakiaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaAxon Neuroscience R&D Services SE, Bratislava, SlovakiaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaAxon Neuroscience R&D Services SE, Bratislava, SlovakiaInstitute of Neuroimmunology, Slovak Academy of Sciences, Bratislava, SlovakiaAxon Neuroscience R&D Services SE, Bratislava, SlovakiaAlzheimer’s disease (AD), the most common tauopathy, is an age-dependent, progressive neurodegenerative disease. Epidemiological studies implicate the role of genetic background in the onset and progression of AD. Despite mutations in familial AD, several risk factors have been implicated in sporadic AD, of which the onset is unknown. In AD, there is a sequential and hierarchical spread of tau pathology to other brain areas. Studies have strived to understand the factors that influence this characteristic spread. Using transgenic rat models with different genetic backgrounds, we reported that the genetic background may influence the manifestation of neurofibrillary pathology. In this study we investigated whether genetic background has an influence in the spread of tau pathology, using hippocampal inoculations of insoluble tau from AD brains in rodent models of tauopathy with either a spontaneously hypertensive (SHR72) or Wistar-Kyoto (WKY72) genetic background. We observed that insoluble tau from human AD induced AT8-positive neurofibrillary structures in the hippocampus of both lines. However, there was no significant difference in the amount of neurofibrillary structures, but the extent of spread was prominent in the W72 line. On the other hand, we observed significantly higher levels of AT8-positive structures in the parietal and frontal cortical areas in W72 when compared to SHR72. Interestingly, we also observed that the microglia in these brain areas in W72 were predominantly phagocytic in morphology (62.4% in parietal and 47.3% in frontal), while in SHR72 the microglia were either reactive or ramified (67.2% in parietal and 84.7% in frontal). The microglia in the hippocampus and occipital cortex in both lines were reactive or ramified structures. Factors such as gender or age are not responsible for the differences observed in these animals. Put together, our results, for the first time, show that the immune response modulating genetic variability is one of the factors that influences the propagation of tau neurofibrillary pathology.https://www.frontiersin.org/article/10.3389/fnagi.2019.00343/fulltauopathyneurofibrillary tanglesmicrogliagenetic backgroundramified |
| spellingShingle | Tomas Smolek Tomas Smolek Veronika Cubinkova Veronika Cubinkova Veronika Brezovakova Bernadeta Valachova Peter Szalay Peter Szalay Norbert Zilka Norbert Zilka Santosh Jadhav Santosh Jadhav Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy Frontiers in Aging Neuroscience tauopathy neurofibrillary tangles microglia genetic background ramified |
| title | Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy |
| title_full | Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy |
| title_fullStr | Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy |
| title_full_unstemmed | Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy |
| title_short | Genetic Background Influences the Propagation of Tau Pathology in Transgenic Rodent Models of Tauopathy |
| title_sort | genetic background influences the propagation of tau pathology in transgenic rodent models of tauopathy |
| topic | tauopathy neurofibrillary tangles microglia genetic background ramified |
| url | https://www.frontiersin.org/article/10.3389/fnagi.2019.00343/full |
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