Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathology
Abstract Background Choroid plexus (CP) or blood-cerebrospinal fluid-barrier (BCSFB) is a unique functional tissue which lines the brain’s fluid-filled ventricles, with a crucial role in CSF production and clearance. BCSFB dysfunction is thought to contribute to toxic protein build-up in neurodegene...
Saved in:
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-12-01
|
| Series: | Fluids and Barriers of the CNS |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12987-024-00597-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849220595859849216 |
|---|---|
| author | Charith Perera Renata Cruz Noam Shemesh Tânia Carvalho David L. Thomas Jack Wells Andrada Ianuș |
| author_facet | Charith Perera Renata Cruz Noam Shemesh Tânia Carvalho David L. Thomas Jack Wells Andrada Ianuș |
| author_sort | Charith Perera |
| collection | DOAJ |
| description | Abstract Background Choroid plexus (CP) or blood-cerebrospinal fluid-barrier (BCSFB) is a unique functional tissue which lines the brain’s fluid-filled ventricles, with a crucial role in CSF production and clearance. BCSFB dysfunction is thought to contribute to toxic protein build-up in neurodegenerative disorders, including Alzheimer’s disease (AD). However, the dynamics of this process remain unknown, mainly due to the paucity of in-vivo methods for assessing CP function. Methods We harness recent developments in Arterial Spin Labelling MRI to measure water delivery across the BCSFB as a proxy for CP function, as well as cerebral blood flow (CBF), at different stages of AD in the widely used triple transgenic mouse model (3xTg), with ages between 8 and 32 weeks. We further compared the MRI results with Y-maze behaviour testing, and histologically validated the expected pathological changes, which recapitulate both amyloid and tau deposition. Results Total BCSFB-mediated water delivery is significantly higher in 3xTg mice (> 50%) from 8 weeks (preclinical stage), an increase which is not explained by differences in ventricular volumes, while tissue parameters such as CBF and T1 are not different between groups at all ages. Behaviour differences between the groups were observed starting at 20 weeks, especially in terms of locomotion, with 3xTg animals showing a significantly smaller number of arm entries in the Y-maze. Conclusions Our work strongly suggests the involvement of CP in the early stages of AD, before the onset of symptoms and behavioural changes, providing a potential biomarker of pathology. |
| format | Article |
| id | doaj-art-bc70a9c3a0384b53aa0d7cdbc0be1eab |
| institution | Kabale University |
| issn | 2045-8118 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Fluids and Barriers of the CNS |
| spelling | doaj-art-bc70a9c3a0384b53aa0d7cdbc0be1eab2024-12-08T12:41:40ZengBMCFluids and Barriers of the CNS2045-81182024-12-0121111510.1186/s12987-024-00597-7Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathologyCharith Perera0Renata Cruz1Noam Shemesh2Tânia Carvalho3David L. Thomas4Jack Wells5Andrada Ianuș6UCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College LondonChampalimaud Research, Champalimaud FoundationChampalimaud Research, Champalimaud FoundationChampalimaud Research, Champalimaud FoundationNeuroradiological Academic Unit, Department of Brain Repair and Rehabilitation, UCL Queen Square Institute of NeurologyUCL Centre for Advanced Biomedical Imaging, Division of Medicine, University College LondonChampalimaud Research, Champalimaud FoundationAbstract Background Choroid plexus (CP) or blood-cerebrospinal fluid-barrier (BCSFB) is a unique functional tissue which lines the brain’s fluid-filled ventricles, with a crucial role in CSF production and clearance. BCSFB dysfunction is thought to contribute to toxic protein build-up in neurodegenerative disorders, including Alzheimer’s disease (AD). However, the dynamics of this process remain unknown, mainly due to the paucity of in-vivo methods for assessing CP function. Methods We harness recent developments in Arterial Spin Labelling MRI to measure water delivery across the BCSFB as a proxy for CP function, as well as cerebral blood flow (CBF), at different stages of AD in the widely used triple transgenic mouse model (3xTg), with ages between 8 and 32 weeks. We further compared the MRI results with Y-maze behaviour testing, and histologically validated the expected pathological changes, which recapitulate both amyloid and tau deposition. Results Total BCSFB-mediated water delivery is significantly higher in 3xTg mice (> 50%) from 8 weeks (preclinical stage), an increase which is not explained by differences in ventricular volumes, while tissue parameters such as CBF and T1 are not different between groups at all ages. Behaviour differences between the groups were observed starting at 20 weeks, especially in terms of locomotion, with 3xTg animals showing a significantly smaller number of arm entries in the Y-maze. Conclusions Our work strongly suggests the involvement of CP in the early stages of AD, before the onset of symptoms and behavioural changes, providing a potential biomarker of pathology.https://doi.org/10.1186/s12987-024-00597-7Alzheimer’s diseaseChoroid plexusBlood CSF barrierBrain perfusionArterial spin labelling MRI3xTg mouse model |
| spellingShingle | Charith Perera Renata Cruz Noam Shemesh Tânia Carvalho David L. Thomas Jack Wells Andrada Ianuș Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathology Fluids and Barriers of the CNS Alzheimer’s disease Choroid plexus Blood CSF barrier Brain perfusion Arterial spin labelling MRI 3xTg mouse model |
| title | Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathology |
| title_full | Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathology |
| title_fullStr | Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathology |
| title_full_unstemmed | Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathology |
| title_short | Non-invasive MRI of blood-cerebrospinal fluid-barrier function in a mouse model of Alzheimer’s disease: a potential biomarker of early pathology |
| title_sort | non invasive mri of blood cerebrospinal fluid barrier function in a mouse model of alzheimer s disease a potential biomarker of early pathology |
| topic | Alzheimer’s disease Choroid plexus Blood CSF barrier Brain perfusion Arterial spin labelling MRI 3xTg mouse model |
| url | https://doi.org/10.1186/s12987-024-00597-7 |
| work_keys_str_mv | AT charithperera noninvasivemriofbloodcerebrospinalfluidbarrierfunctioninamousemodelofalzheimersdiseaseapotentialbiomarkerofearlypathology AT renatacruz noninvasivemriofbloodcerebrospinalfluidbarrierfunctioninamousemodelofalzheimersdiseaseapotentialbiomarkerofearlypathology AT noamshemesh noninvasivemriofbloodcerebrospinalfluidbarrierfunctioninamousemodelofalzheimersdiseaseapotentialbiomarkerofearlypathology AT taniacarvalho noninvasivemriofbloodcerebrospinalfluidbarrierfunctioninamousemodelofalzheimersdiseaseapotentialbiomarkerofearlypathology AT davidlthomas noninvasivemriofbloodcerebrospinalfluidbarrierfunctioninamousemodelofalzheimersdiseaseapotentialbiomarkerofearlypathology AT jackwells noninvasivemriofbloodcerebrospinalfluidbarrierfunctioninamousemodelofalzheimersdiseaseapotentialbiomarkerofearlypathology AT andradaianus noninvasivemriofbloodcerebrospinalfluidbarrierfunctioninamousemodelofalzheimersdiseaseapotentialbiomarkerofearlypathology |