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Measuring the Permeability of the Blood-Brain Barrier in Alzheimer's Disease Using Dynamic Contrast Enhanced MRI

Published online by Cambridge University Press:  07 July 2023

Beth McCausland*
Affiliation:
University of Southampton, Southampton, United Kingdom Southern Health NHS Foundation Trust, Southampton, United Kingdom University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Nathan Huneke
Affiliation:
University of Southampton, Southampton, United Kingdom Southern Health NHS Foundation Trust, Southampton, United Kingdom
Aravinthan Varatharaj
Affiliation:
University of Southampton, Southampton, United Kingdom University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Claire Gee
Affiliation:
University of Southampton, Southampton, United Kingdom Southern Health NHS Foundation Trust, Southampton, United Kingdom
Amy Kunicki
Affiliation:
University of Southampton, Southampton, United Kingdom Southern Health NHS Foundation Trust, Southampton, United Kingdom
Angela Darekar
Affiliation:
University of Southampton, Southampton, United Kingdom University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Jessica Teeling
Affiliation:
University of Southampton, Southampton, United Kingdom University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Henrik Zetterberg
Affiliation:
UK Dementia Research Institute at University College London, University College London Queen Square Institute of Neurology, London, United Kingdom
Clive Holmes
Affiliation:
University of Southampton, Southampton, United Kingdom Southern Health NHS Foundation Trust, Southampton, United Kingdom
Ian Galea
Affiliation:
University of Southampton, Southampton, United Kingdom University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
Jay Amin
Affiliation:
University of Southampton, Southampton, United Kingdom Southern Health NHS Foundation Trust, Southampton, United Kingdom
*
*Corresponding author.
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Abstract

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Aims

1) To compare blood brain barrier (BBB) permeability between AD and controls. 2) To examine the relationship between BBB permeability and cognitive decline in AD. 3) To examine the relationship between BBB permeability and peripheral markers of inflammation.

Methods

This pilot study combines the use whole brain DCE-MRI, with measures of peripheral inflammation in serum and urine. This is a clinical cohort study with longitudinal and cross-sectional arms, involving n = 15 AD and n = 17 age and gender matched controls. BBB permeability is measured using DCE-MRI and inflammation is measured by comparing serum cytokine and urine neopterin concentrations. AD participants attend three study visits over 12 months; control participants attend two over one week. Urinary neopterin analysis is being conducted in February 2023.The 12 month follow up visits complete in May 2023. Both neopterin and longitudinal cognitive assessment data will be included in the poster presentation in July.

Results

AD and control groups were well matched with no significant differences in demographics and multi-morbidity. We measured blood cytokine profiles for IL-6, IL-8, IL-2, IL-4, IL-1b, IL-10, IL13, IL-12p70-, TNF-alpha and INF-gamma. Only INF-Gamma was significantly different; higher in AD vs Controls (mean ± SD; 28.758 ± 90.226 AD, 3.773 ± 2.256 Control, P = 0.03). There were no significant differences in markers of neurodegeneration NfL and pTau-181, or vascular markers VCAM1, ICAM1, CRP and SAA between the groups. Ki is being calculated for overall whole brain, white matter, grey matter and hippocampus regions; an interim analysis showed no significant differences between the tissue categories, but analysis is ongoing.

Conclusion

There are currently no prognostic biomarkers that accurately predict decline in AD. We believe this pilot study will add to the literature about the utility and feasibility of DCE-MRI to measure BBB permeability. We hope that combining DCE-MRI with blood and urine biomarkers will further our knowledge of the pathophysiology of AD and help to develop minimally invasive biomarkers for identifying patients with AD, including those who are at risk of faster progression.

Type
Research
Creative Commons
Creative Common License - CCCreative Common License - BYCreative Common License - NC
This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http://creativecommons.org/licenses/by-nc/4.0), which permits unrestricted re-use, distribution, and reproduction in any medium, provided the original work is properly cited. This does not need to be placed under each abstract, just each page is fine.
Copyright
Copyright © The Author(s), 2023. Published by Cambridge University Press on behalf of the Royal College of Psychiatrists

Footnotes

Abstracts were reviewed by the RCPsych Academic Faculty rather than by the standard BJPsych Open peer review process and should not be quoted as peer-reviewed by BJPsych Open in any subsequent publication.

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