학술논문
Developing blood-brain barrier arterial spin labelling as a non-invasive early biomarker of Alzheimer’s disease (DEBBIE-AD): a prospective observational multicohort study protocol
Document Type
article
Author
Catherine Morgan; Frederik Barkhof; David L Thomas; Saima Hilal; Moritz Brandt; Betty M Tijms; Majon Muller; Tormod Fladby; Jennifer Linn; Per Selnes; Atle Bjørnerud; Elsmarieke M van de Giessen; Beatriz Padrela; Amnah Mahroo; Mervin Tee; Markus H Sneve; Paulien Moyaert; Oliver Geier; Joost P A Kuijer; Soetkin Beun; Wibeke Nordhøy; Yufei David Zhu; Mareike A Buck; Daniel C Hoinkiss; Simon Konstandin; Jörn Huber; Julia Wiersinga; Roos Rikken; Diederick de Leeuw; Håkon Grydeland; Lynette Tippett; Erin E Cawston; Esin Ozturk-Isik; Anders Fjell; Kristine Walhovd; Lene Pålhaugen; Patricia Clement; Eric Achten; Udunna Anazodo; Klaus Eickel; Jan Petr; Matthias Günther; Henk J M M Mutsaerts
Source
BMJ Open, Vol 14, Iss 3 (2024)
Subject
Language
English
ISSN
2044-6055
Abstract
Introduction Loss of blood-brain barrier (BBB) integrity is hypothesised to be one of the earliest microvascular signs of Alzheimer’s disease (AD). Existing BBB integrity imaging methods involve contrast agents or ionising radiation, and pose limitations in terms of cost and logistics. Arterial spin labelling (ASL) perfusion MRI has been recently adapted to map the BBB permeability non-invasively. The DEveloping BBB-ASL as a non-Invasive Early biomarker (DEBBIE) consortium aims to develop this modified ASL-MRI technique for patient-specific and robust BBB permeability assessments. This article outlines the study design of the DEBBIE cohorts focused on investigating the potential of BBB-ASL as an early biomarker for AD (DEBBIE-AD).Methods and analysis DEBBIE-AD consists of a multicohort study enrolling participants with subjective cognitive decline, mild cognitive impairment and AD, as well as age-matched healthy controls, from 13 cohorts. The precision and accuracy of BBB-ASL will be evaluated in healthy participants. The clinical value of BBB-ASL will be evaluated by comparing results with both established and novel AD biomarkers. The DEBBIE-AD study aims to provide evidence of the ability of BBB-ASL to measure BBB permeability and demonstrate its utility in AD and AD-related pathologies.Ethics and dissemination Ethics approval was obtained for 10 cohorts, and is pending for 3 cohorts. The results of the main trial and each of the secondary endpoints will be submitted for publication in a peer-reviewed journal.