Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease
Abstract Traumatic brain injury (TBI) has emerged as a significant risk factor for Alzheimer’s disease (AD), a complex and devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Both conditions share a common feature: blood‒brain barrier (BBB) dysfunct...
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| Format: | Article |
| Language: | English |
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BMC
2025-03-01
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| Series: | Translational Neurodegeneration |
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| Online Access: | https://doi.org/10.1186/s40035-025-00478-5 |
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| author | Bryan Sun Lulin Li Odette A. Harris Jian Luo |
| author_facet | Bryan Sun Lulin Li Odette A. Harris Jian Luo |
| author_sort | Bryan Sun |
| collection | DOAJ |
| description | Abstract Traumatic brain injury (TBI) has emerged as a significant risk factor for Alzheimer’s disease (AD), a complex and devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Both conditions share a common feature: blood‒brain barrier (BBB) dysfunction, which is believed to play a pivotal role in linking TBI to the development of AD. This review delves into the intricate relationship between TBI and AD, with a focus on BBB dysfunction and its critical role in disease mechanisms and therapeutic development. We first present recent evidence from epidemiological studies highlighting the increased incidence of AD among individuals with a history of TBI, as well as pathological and animal model studies that demonstrate how TBI can accelerate AD-like pathology. Next, we explore the mechanisms by which BBB dysfunction may mediate TBI-induced AD pathology. Finally, we investigate the shared molecular pathways associated with BBB dysfunction in both TBI and AD conditions and discuss the latest findings on how targeting these pathways and employing regenerative approaches, such as stem cell therapy and pharmacological interventions, can enhance BBB function and mitigate neurodegeneration. |
| format | Article |
| id | doaj-art-9f93edcd293b40e3b1a8d04688f38b10 |
| institution | OA Journals |
| issn | 2047-9158 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Translational Neurodegeneration |
| spelling | doaj-art-9f93edcd293b40e3b1a8d04688f38b102025-08-20T02:10:20ZengBMCTranslational Neurodegeneration2047-91582025-03-0114112210.1186/s40035-025-00478-5Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's diseaseBryan Sun0Lulin Li1Odette A. Harris2Jian Luo3Palo Alto Veterans Institute for Research, VA Palo Alto Health Care SystemPalo Alto Veterans Institute for Research, VA Palo Alto Health Care SystemDepartment of Neurosurgery, Stanford University School of MedicinePalo Alto Veterans Institute for Research, VA Palo Alto Health Care SystemAbstract Traumatic brain injury (TBI) has emerged as a significant risk factor for Alzheimer’s disease (AD), a complex and devastating neurodegenerative disorder characterized by progressive cognitive decline and memory loss. Both conditions share a common feature: blood‒brain barrier (BBB) dysfunction, which is believed to play a pivotal role in linking TBI to the development of AD. This review delves into the intricate relationship between TBI and AD, with a focus on BBB dysfunction and its critical role in disease mechanisms and therapeutic development. We first present recent evidence from epidemiological studies highlighting the increased incidence of AD among individuals with a history of TBI, as well as pathological and animal model studies that demonstrate how TBI can accelerate AD-like pathology. Next, we explore the mechanisms by which BBB dysfunction may mediate TBI-induced AD pathology. Finally, we investigate the shared molecular pathways associated with BBB dysfunction in both TBI and AD conditions and discuss the latest findings on how targeting these pathways and employing regenerative approaches, such as stem cell therapy and pharmacological interventions, can enhance BBB function and mitigate neurodegeneration.https://doi.org/10.1186/s40035-025-00478-5Blood–brain barrierTraumatic brain injuryAlzheimer’s diseaseNeuroinflammationNeurodegeneration |
| spellingShingle | Bryan Sun Lulin Li Odette A. Harris Jian Luo Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease Translational Neurodegeneration Blood–brain barrier Traumatic brain injury Alzheimer’s disease Neuroinflammation Neurodegeneration |
| title | Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease |
| title_full | Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease |
| title_fullStr | Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease |
| title_full_unstemmed | Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease |
| title_short | Blood–brain barrier disruption: a pervasive driver and mechanistic link between traumatic brain injury and Alzheimer's disease |
| title_sort | blood brain barrier disruption a pervasive driver and mechanistic link between traumatic brain injury and alzheimer s disease |
| topic | Blood–brain barrier Traumatic brain injury Alzheimer’s disease Neuroinflammation Neurodegeneration |
| url | https://doi.org/10.1186/s40035-025-00478-5 |
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