Water-exchange MRI detects subtle blood-brain barrier breakdown in Alzheimer's disease rats

NeuroImage
Ben R DickieGeoff J M Parker

Abstract

Blood-brain barrier (BBB) breakdown has been hypothesized to play a key role in the onset and progression of Alzheimer's disease (AD). However, the question of whether AD itself contributes to loss of BBB integrity is still uncertain, as many in-vivo studies have failed to detect signs of AD-related BBB breakdown. We hypothesize AD-related BBB damage is subtle, and that these negative results arise from a lack of measurement sensitivity. With the aim of developing a more sensitive measure of BBB breakdown, we have designed a novel MRI scanning protocol to quantify the trans-BBB exchange of endogenous water. Using this method, we detect increased BBB water permeability in a rat model of AD that is associated with reduced expression of the tight junction protein occludin. BBB permeability to MRI contrast agent, assessed using dynamic contrast-enhanced (DCE)-MRI, did not differ between transgenic and wild-type animals and was uncorrelated with occludin expression. Our data supports the occurrence of AD-related BBB breakdown, and indicates that such BBB pathology is subtle and may be undetectable using existing 'tracer leakage' methods. Our validated water-exchange MRI method provides a new powerful tool with which to study BBB dam...Continue Reading

Citations

Jul 17, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Wenlan GuanKezheng Chen
Mar 14, 2020·Journal of Magnetic Resonance Imaging : JMRI·Ruiliang BaiYingchao Liu
Jun 20, 2020·Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging·Valerie C AndersonWilliam D Rooney
Sep 11, 2020·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Yolanda OheneJack A Wells
Sep 16, 2020·Investigative Radiology·Elles P ElschotJacobus F A Jansen
Feb 10, 2021·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Zixuan LinHanzhang Lu
Feb 1, 2021·Chemico-biological Interactions·Jiangping WeiDayue Darrel Duan
May 19, 2021·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Cameron ManningMichael J Thrippleton
May 28, 2021·Annals of Neurology·Zixuan LinHanzhang Lu
Jun 3, 2021·International Journal of Molecular Sciences·Chia-Yuan ChangWen-Sung Lai
Aug 7, 2021·Journal of Neuroimaging : Official Journal of the American Society of Neuroimaging·Ian J TaggeWilliam D Rooney
Dec 21, 2021·Frontiers in Neuroscience·Amnah MahrooMatthias Günther

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.

Alzheimer's Disease: Neuroimaging

Neuroimaging can help identify pathological hallmarks of Alzheimer's disease (AD). Here is the latest research on neuroimaging modalities, including magnetic resonance imaging and positron emission tomography, in AD.

© 2022 Meta ULC. All rights reserved