Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease
Abstract Background Despite being a brain disorder, Alzheimer's disease (AD) is often accompanied by peripheral organ dysregulations (e.g., loss of bladder control in late‐stage AD), which highly rely on spinal cord coordination. However, the causal factor(s) for peripheral organ dysregulation...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-07-01
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| Series: | Clinical and Translational Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/ctm2.1332 |
| _version_ | 1797771135354404864 |
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| author | Sijia He Shulan Qiu Meixia Pan Juan P. Palavicini Hu Wang Xin Li Anindita Bhattacharjee Savannah Barannikov Kevin F. Bieniek Jeffrey L. Dupree Xianlin Han |
| author_facet | Sijia He Shulan Qiu Meixia Pan Juan P. Palavicini Hu Wang Xin Li Anindita Bhattacharjee Savannah Barannikov Kevin F. Bieniek Jeffrey L. Dupree Xianlin Han |
| author_sort | Sijia He |
| collection | DOAJ |
| description | Abstract Background Despite being a brain disorder, Alzheimer's disease (AD) is often accompanied by peripheral organ dysregulations (e.g., loss of bladder control in late‐stage AD), which highly rely on spinal cord coordination. However, the causal factor(s) for peripheral organ dysregulation in AD remain elusive. Methods The central nervous system (CNS) is enriched in lipids. We applied quantitative shotgun lipidomics to determine lipid profiles of human AD spinal cord tissues. Additionally, a CNS sulfatide (ST)‐deficient mouse model was used to study the lipidome, transcriptome and peripheral organ phenotypes of ST loss. Results We observed marked myelin lipid reduction in the spinal cord of AD subjects versus cognitively normal individuals. Among which, levels of ST, a myelin‐enriched lipid class, were strongly and negatively associated with the severity of AD. A CNS myelin‐specific ST‐deficient mouse model was used to further identify the causes and consequences of spinal cord lipidome changes. Interestingly, ST deficiency led to spinal cord lipidome and transcriptome profiles highly resembling those observed in AD, characterized by decline of multiple myelin‐enriched lipid classes and enhanced inflammatory responses, respectively. These changes significantly disrupted spinal cord function and led to substantial enlargement of urinary bladder in ST‐deficient mice. Conclusions Our study identified CNS ST deficiency as a causal factor for AD‐like lipid dysregulation, inflammation response and ultimately the development of bladder disorders. Targeting to maintain ST levels may serve as a promising strategy for the prevention and treatment of AD‐related peripheral disorders. |
| first_indexed | 2024-03-12T21:33:10Z |
| format | Article |
| id | doaj.art-0d768f66a1884131945072162b73e1a2 |
| institution | Directory Open Access Journal |
| issn | 2001-1326 |
| language | English |
| last_indexed | 2024-03-12T21:33:10Z |
| publishDate | 2023-07-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical and Translational Medicine |
| spelling | doaj.art-0d768f66a1884131945072162b73e1a22023-07-27T15:20:29ZengWileyClinical and Translational Medicine2001-13262023-07-01137n/an/a10.1002/ctm2.1332Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's diseaseSijia He0Shulan Qiu1Meixia Pan2Juan P. Palavicini3Hu Wang4Xin Li5Anindita Bhattacharjee6Savannah Barannikov7Kevin F. Bieniek8Jeffrey L. Dupree9Xianlin Han10Barshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSABarshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSABarshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSABarshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSABarshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSABarshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSABarshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSADepartment of Pathology Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health San Antonio San AntonioTexasUSADepartment of Pathology Glenn Biggs Institute for Alzheimer's and Neurodegenerative Diseases University of Texas Health San Antonio San AntonioTexasUSADepartment of Anatomy and Neurobiology Virginia Commonwealth University RichmondVirginiaUSABarshop Institute for Longevity and Aging Studies University of Texas Health San Antonio San AntonioTexasUSAAbstract Background Despite being a brain disorder, Alzheimer's disease (AD) is often accompanied by peripheral organ dysregulations (e.g., loss of bladder control in late‐stage AD), which highly rely on spinal cord coordination. However, the causal factor(s) for peripheral organ dysregulation in AD remain elusive. Methods The central nervous system (CNS) is enriched in lipids. We applied quantitative shotgun lipidomics to determine lipid profiles of human AD spinal cord tissues. Additionally, a CNS sulfatide (ST)‐deficient mouse model was used to study the lipidome, transcriptome and peripheral organ phenotypes of ST loss. Results We observed marked myelin lipid reduction in the spinal cord of AD subjects versus cognitively normal individuals. Among which, levels of ST, a myelin‐enriched lipid class, were strongly and negatively associated with the severity of AD. A CNS myelin‐specific ST‐deficient mouse model was used to further identify the causes and consequences of spinal cord lipidome changes. Interestingly, ST deficiency led to spinal cord lipidome and transcriptome profiles highly resembling those observed in AD, characterized by decline of multiple myelin‐enriched lipid classes and enhanced inflammatory responses, respectively. These changes significantly disrupted spinal cord function and led to substantial enlargement of urinary bladder in ST‐deficient mice. Conclusions Our study identified CNS ST deficiency as a causal factor for AD‐like lipid dysregulation, inflammation response and ultimately the development of bladder disorders. Targeting to maintain ST levels may serve as a promising strategy for the prevention and treatment of AD‐related peripheral disorders.https://doi.org/10.1002/ctm2.1332Alzheimer's diseasebladderlipidomespinal cordsulfatide |
| spellingShingle | Sijia He Shulan Qiu Meixia Pan Juan P. Palavicini Hu Wang Xin Li Anindita Bhattacharjee Savannah Barannikov Kevin F. Bieniek Jeffrey L. Dupree Xianlin Han Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease Clinical and Translational Medicine Alzheimer's disease bladder lipidome spinal cord sulfatide |
| title | Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease |
| title_full | Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease |
| title_fullStr | Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease |
| title_full_unstemmed | Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease |
| title_short | Central nervous system sulfatide deficiency as a causal factor for bladder disorder in Alzheimer's disease |
| title_sort | central nervous system sulfatide deficiency as a causal factor for bladder disorder in alzheimer s disease |
| topic | Alzheimer's disease bladder lipidome spinal cord sulfatide |
| url | https://doi.org/10.1002/ctm2.1332 |
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