A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau
Abstract Background Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pa...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Alzheimer’s Research & Therapy |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13195-024-01392-0 |
| _version_ | 1797276713596485632 |
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| author | Zhouquan Jiang Jing Wang Yongpeng Qin Shanggong Liu Bin Luo Fan Bai Huiyi Wei Shaojuan Zhang Junjie Wei Guoyu Ding Long Ma Shu He Rongjie Chen Ying Sun Yi Chen Lu Wang Hao Xu Xiangyu Wang Gong Chen Wenliang Lei |
| author_facet | Zhouquan Jiang Jing Wang Yongpeng Qin Shanggong Liu Bin Luo Fan Bai Huiyi Wei Shaojuan Zhang Junjie Wei Guoyu Ding Long Ma Shu He Rongjie Chen Ying Sun Yi Chen Lu Wang Hao Xu Xiangyu Wang Gong Chen Wenliang Lei |
| author_sort | Zhouquan Jiang |
| collection | DOAJ |
| description | Abstract Background Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys. Methods Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests. Results We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents. Conclusions This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2 ~ 3 months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD. |
| first_indexed | 2024-03-07T15:32:11Z |
| format | Article |
| id | doaj.art-e7be54b9658f4d4eb0ea86e578151b24 |
| institution | Directory Open Access Journal |
| issn | 1758-9193 |
| language | English |
| last_indexed | 2024-03-07T15:32:11Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Alzheimer’s Research & Therapy |
| spelling | doaj.art-e7be54b9658f4d4eb0ea86e578151b242024-03-05T16:22:07ZengBMCAlzheimer’s Research & Therapy1758-91932024-01-0116112410.1186/s13195-024-01392-0A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tauZhouquan Jiang0Jing Wang1Yongpeng Qin2Shanggong Liu3Bin Luo4Fan Bai5Huiyi Wei6Shaojuan Zhang7Junjie Wei8Guoyu Ding9Long Ma10Shu He11Rongjie Chen12Ying Sun13Yi Chen14Lu Wang15Hao Xu16Xiangyu Wang17Gong Chen18Wenliang Lei19Guangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityDepartment of Neurosurgery, the First Affiliated Hospital, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityDepartment of Nuclear Medicine and PET/CT-MRI Centre, the First Affiliated Hospital, Jinan UniversityDepartment of Nuclear Medicine and PET/CT-MRI Centre, the First Affiliated Hospital, Jinan UniversityDepartment of Nuclear Medicine and PET/CT-MRI Centre, the First Affiliated Hospital, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityDepartment of Nuclear Medicine and PET/CT-MRI Centre, the First Affiliated Hospital, Jinan UniversityDepartment of Nuclear Medicine and PET/CT-MRI Centre, the First Affiliated Hospital, Jinan UniversityDepartment of Neurosurgery, the First Affiliated Hospital, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityGuangdong-Hong Kong-Macau Institute of CNS Regeneration, Jinan UniversityAbstract Background Alzheimer’s disease (AD) is one of the most burdening diseases of the century with no disease-modifying treatment at this time. Nonhuman primates (NHPs) share genetic, anatomical, and physiological similarities with humans, making them ideal model animals for investigating the pathogenesis of AD and potential therapies. However, the use of NHPs in AD research has been hindered by the paucity of AD monkey models due to their long generation time, ethical considerations, and technical challenges in genetically modifying monkeys. Methods Here, we developed an AD-like NHP model by overexpressing human tau in the bilateral hippocampi of adult rhesus macaque monkeys. We evaluated the pathological features of these monkeys with immunostaining, Nissl staining, cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), positron emission tomography (PET), and behavioural tests. Results We demonstrated that after hippocampal overexpression of tau protein, these monkeys displayed multiple pathological features of AD, including 3-repeat (3R)/4-repeat (4R) tau accumulation, tau hyperphosphorylation, tau propagation, neuronal loss, hippocampal atrophy, neuroinflammation, Aβ clearance deficits, blood vessel damage, and cognitive decline. More interestingly, the accumulation of both 3R and 4R tau is specific to NHPs but not found in adult rodents. Conclusions This work establishes a tau-induced AD-like NHP model with many key pathological and behavioural features of AD. In addition, our model may potentially become one of the AD NHP models adopted by researchers worldwide since it can be generated within 2 ~ 3 months through a single injection of AAVs into the monkey brains. Hence, our model NHPs may facilitate mechanistic studies and therapeutic treatments for AD.https://doi.org/10.1186/s13195-024-01392-0Alzheimer’s diseaseHuman tau3R tau4R tauTau hyperphosphorylationNonhuman primate |
| spellingShingle | Zhouquan Jiang Jing Wang Yongpeng Qin Shanggong Liu Bin Luo Fan Bai Huiyi Wei Shaojuan Zhang Junjie Wei Guoyu Ding Long Ma Shu He Rongjie Chen Ying Sun Yi Chen Lu Wang Hao Xu Xiangyu Wang Gong Chen Wenliang Lei A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau Alzheimer’s Research & Therapy Alzheimer’s disease Human tau 3R tau 4R tau Tau hyperphosphorylation Nonhuman primate |
| title | A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau |
| title_full | A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau |
| title_fullStr | A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau |
| title_full_unstemmed | A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau |
| title_short | A nonhuman primate model with Alzheimer’s disease-like pathology induced by hippocampal overexpression of human tau |
| title_sort | nonhuman primate model with alzheimer s disease like pathology induced by hippocampal overexpression of human tau |
| topic | Alzheimer’s disease Human tau 3R tau 4R tau Tau hyperphosphorylation Nonhuman primate |
| url | https://doi.org/10.1186/s13195-024-01392-0 |
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