Alzheimer's disease pathology is associated with earlier alterations to blood–brain barrier water permeability compared with healthy ageing in TgF344‐AD rats

Dickie, Ben; Boutin, Hervé; Parker, Geoff J.M.; Parkes, Laura M.

doi:10.1002/nbm.4510

Cited by 30 publications

(28 citation statements)

References 36 publications

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“…Dickie et al reported that DCE-MRI failed to detect the difference between the TgF344 rats and wild-type rats at 18 months-of-age and that the increased BBB water permeability was detected by using multi-flip angle multi-echo (MFAME) water-exchange MRI in TgF344 rats compared to wild-type rats [ 245 ]. Using the same method, Dickie et al further showed in a cross-sectional study that BBB water permeability was affected earlier in TgF344 rats (13–18 months-of-age) compared to that in wild-type rats in normal ageing (18–21 months-of-age) [ 246 ]. Further studies are required to establish non-invasive imaging tools for visualizing BBB integrity and to elucidate the degree of BBB impairment in AD animal models.…”

Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

2021

IJMS

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Amyloid-beta (Aβ) plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant Aβ accumulation induces neuroinflammation, cerebrovascular alterations, and synaptic deficits, leading to cognitive impairment. Animal models recapitulating the Aβ pathology, such as transgenic, knock-in mouse and rat models, have facilitated the understanding of disease mechanisms and the development of therapeutics targeting Aβ. There is a rapid advance in high-field MRI in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences, such as diffusion tensor imaging, arterial spin labeling, resting-state functional MRI, anatomical MRI, and MR spectroscopy, as well as contrast agents, have been developed for preclinical imaging in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole-brain field of view. MRI has been used to visualize non-invasively the Aβ deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, and cerebrovascular and glymphatic system in animal models of Alzheimer’s disease amyloidosis. Many of the readouts are translational toward clinical MRI applications in patients with Alzheimer’s disease. In this review, we summarize the recent advances in MRI for visualizing the pathophysiology in amyloidosis animal models. We discuss the outstanding challenges in brain imaging using MRI in small animals and propose future outlook in visualizing Aβ-related alterations in the brains of animal models.

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Section: Discussionmentioning

confidence: 99%

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

2021

IJMS

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“…We have recently used this experimental approach to report WM k po decreases with HC aging 12 . Other investigators have reported BBB water permeability increases in rat brain Alzheimer's disease (AD) models 58,59 . Though the researchers used the same method as here, and measured the k po and v b factors separately, they report only the composite P w S products.…”

Section: Discussionmentioning

confidence: 99%

“… 12 Other investigators have reported BBB water permeability increases in rat brain Alzheimer's disease (AD) models. 58 , 59 Though the researchers used the same method as here, and measured the k po and v b factors separately, they report only the composite P w S products. Thus, it is impossible to know if water permeation does actually increase in AD.…”

Section: Discussionmentioning

confidence: 99%

Gray matter blood‐brain barrier water exchange dynamics are reduced in progressive multiple sclerosis

Tagge

Anderson

Springer

et al. 2021

Journal of Neuroimaging

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Background and Purpose: To compare transcapillary wall water exchange, a putative marker of cerebral metabolic health, in brain T 2 white matter (WM) lesions and normal appearing white and gray matter (NAWM and NAGM, respectively) in individuals with progressive multiple sclerosis (PMS) and healthy controls (HC).Methods: Dynamic-contrast-enhanced 7T MRI data were obtained from 19 HC and 23 PMS participants. High-resolution pharmacokinetic parametric maps representing tissue microvascular and microstructural properties were created by shutter-speed (SS) paradigm modeling to obtain estimates of blood volume fraction (v b ), water molecule capillary efflux rate constant (k po ), and the water capillary wall permeability surface area product (P w S ≡ v b *k po ). Linear regression models were used to investigate differences in (i) k po and P w S between groups in NAWM and NAGM, and (ii) between WM lesions and NAWM in PMS.Results: High-resolution parametric maps were produced to visualize tissue classes and resolve individual WM lesions. Normal-appearing gray matter k po and P w S were significantly decreased in PMS compared to HC (p ≤ .01). Twenty-one T 2 WM lesions were analyzed in 10 participants with PMS. k po was significantly decreased in WM lesions compared to PMS NAWM (p < .0001). Conclusions:Transcapillary water exchange is reduced in PMS NAGM compared to HC and is further reduced in PMS WM lesions, suggesting pathologically impaired brain metabolism. k po provides a sensitive measure of cerebral metabolic activity and/or coupling, and can be mapped at higher spatial resolution than conventional imaging techniques assessing metabolic activity.

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“…Dickie et al reported that DCE-MRI did not detected the difference between the TgF344 and wild-type rats at 18 months-of-age, and that increased BBB water permeability was detected by using multi-flip angle multi-echo (MFAME) water-exchange MRI in TgF344 rats compared to wild-type [203]. Using the same method, Dickie et al further showed in a cross-sectional study that BBB water permeability is affected earlier in TgF344 rats (between 13-18 months-of-age) compared to that in wild-type mice in normal ageing (between 18-21 months-of-age) [204]. Further studies are required to further establish non-invasive imaging tools for visualizing BBB integrity and to elucidate the degree and role of BBB impairment in AD animal models.…”

Section: Discussionmentioning

confidence: 99%

“…[81] T2* Tg SwDI mice [145] T2*w APP23 mice [144] DCE 5×FAD, APOE mice [202] MFAME-DCE TgF344 rats [203,204] T2*w,…”

Section: Declaration Of Interestmentioning

confidence: 99%

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Ni¹

2021

Preprint

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Amyloid-beta plays an important role in the pathogenesis of Alzheimer’s disease. Aberrant amyloid-beta and tau accumulation induce neuroinflammation, cerebrovascular alterations, synaptic deficits, functional deficits, and neurodegeneration, leading to cognitive impairment. Animal models recapitulating the amyloid-beta pathology such as transgenic, knock-in mouse and rat models have facilitated the understanding of disease mechanisms and development of therapeutics targeting at amyloid-beta. There is a rapid advance in high-field MR in small animals. Versatile high-field magnetic resonance imaging (MRI) sequences such as diffusion tensor imaging, arterial spin labelling, resting-state functional MRI, anatomical MRI, MR spectroscopy as well as contrast agents have been developed for the applications in animal models. These tools have enabled high-resolution in vivo structural, functional, and molecular readouts with a whole brain field-of-view. MRI have been utilized to visualize non-invasively the amyloid-beta deposits, synaptic deficits, regional brain atrophy, impairment in white matter integrity, functional connectivity, cerebrovascular and glymphatic system in animal models of amyloidosis. Many of the readouts are translational in clinical MRI in the brain of patients with Alzheimer’s disease. In this review, we summarize the recent advance of using MRI for visualizing the pathophysiology in amyloidosis animal model. We discuss the outstanding challenges in brain imaging using MRI in small animal and propose future outlook in visualizing amyloid-beta-related alterations in brain of animal models.

show abstract

Alzheimer's disease pathology is associated with earlier alterations to blood–brain barrier water permeability compared with healthy ageing in TgF344‐AD rats

Cited by 30 publications

References 36 publications

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

Gray matter blood‐brain barrier water exchange dynamics are reduced in progressive multiple sclerosis

Magnetic Resonance Imaging in Animal Models of Alzheimer’s Disease Amyloidosis

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